482 research outputs found
Functional and Structural Insights Revealed by Molecular Dynamics Simulations of an Essential RNA Editing Ligase in Trypanosoma brucei
- Author
- A Schnaufer
- A Schnaufer
- AD MacKerell
- AH Fairlamb
- AK Panigrahi
- AV Cherepanov
- B Blum
- CE Huang
- CK Ho
- CK Ho
- EA Worthey
- GA Cross
- IT Suydam
- J Deng
- J. Andrew McCammon
- JC Phillips
- Jennifer Keiser
- K Stuart
- KD Stuart
- L Simpson
- L Zhang
- LN Rusche
- ME Noble
- MF Sanner
- Robert V. Swift
- Rommie E. Amaro
- S Feller
- S Shuman
- S Yin
- SD Seiwert
- T Darden
- T Schindler
- WL Jorgensen
- Publication venue
- Public Library of Science
- Publication date
- 01/11/2007
- Field of study
RNA editing ligase 1 (TbREL1) is required for the survival of both the insect and bloodstream forms of Trypanosoma brucei, the parasite responsible for the devastating tropical disease African sleeping sickness. The type of RNA editing that TbREL1 is involved in is unique to the trypanosomes, and no close human homolog is known to exist. In addition, the high-resolution crystal structure revealed several unique features of the active site, making this enzyme a promising target for structure-based drug design. In this work, two 20 ns atomistic molecular dynamics (MD) simulations are employed to investigate the dynamics of TbREL1, both with and without the ATP substrate present. The flexibility of the active site, dynamics of conserved residues and crystallized water molecules, and the interactions between TbREL1 and the ATP substrate are investigated and discussed in the context of TbREL1's function. Differences in local and global motion upon ATP binding suggest that two peripheral loops, unique to the trypanosomes, may be involved in interdomain signaling events. Notably, a significant structural rearrangement of the enzyme's active site occurs during the apo simulations, opening an additional cavity adjacent to the ATP binding site that could be exploited in the development of effective inhibitors directed against this protozoan parasite. Finally, ensemble averaged electrostatics calculations over the MD simulations reveal a novel putative RNA binding site, a discovery that has previously eluded scientists. Ultimately, we use the insights gained through the MD simulations to make several predictions and recommendations, which we anticipate will help direct future experimental studies and structure-based drug discovery efforts against this vital enzyme
Augmentation of Reverse Transcription by Integrase through an Interaction with Host Factor, SIP1/Gemin2 Is Critical for HIV-1 Infection
- Author
- A Adachi
- A Engelman
- A Engelman
- A Mousnier
- AD Leavitt
- AL Brass
- B Taddeo
- BR Cullen
- C Ogawa
- CW Dobard
- D Buhler
- E Devroe
- EA Hehl
- G Maertens
- G Maertens
- G Meister
- GV Kalpana
- H Miyoshi
- Hironori Nishitsuji
- IO Gleenberg
- J Kulkosky
- JA Briggs
- JY Wang
- K Zhu
- L Berthoux
- LQ Al-Mawsawi
- M Cai
- M Llano
- M Llano
- Mari Kannagi
- Masashi Miyano
- MC Shun
- MH Nymark-McMahon
- MH Nymark-McMahon
- N Tsurutani
- P Cherepanov
- P Cherepanov
- P Gallay
- Q Liu
- R Konig
- R Lu
- RA Katz
- S Emiliani
- S Hamamoto
- S Jablonka
- SP Goff
- T Ikeda
- T Masuda
- T Nakamura
- TA Wilkinson
- Takao Masuda
- Takaya Hayashi
- Takuya Takahashi
- TM Jenkins
- U Fischer
- Wang-Shick Ryu
- X Wu
- Y Nomura
- Z Hayouka
- Publication venue
- Public Library of Science
- Publication date
- 01/11/2009
- Field of study
There has been accumulating evidence for the involvement of retroviral integrase (IN) in the reverse transcription of viral RNA. We previously identified a host factor, survival motor neuron-interacting protein 1 (SIP1/Gemin2) that binds to human immunodeficiency virus type 1 (HIV-1) IN and supports HIV-1 infection apparently at reverse transcription step. Here, we demonstrated that HIV-1 IN together with SIP1 augments reverse transcriptase (RT) activity by enhancing the assembly of RT on viral RNA in vitro. Synthetic peptides corresponding to the binding motifs within IN that inhibited the IN-SIP1 interaction abrogated reverse transcription in vitro and in vivo. Furthermore, knockdown of SIP1 reduced intracellular stability and multimer formation of IN through proteasome-mediated degradation machinery. Taken together, SIP1 appears to stabilize functional multimer forms of IN, thereby promoting the assembly of IN and RT on viral RNA to allow efficient reverse transcription, which is a prerequisite for efficient HIV-1 infection
Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV
- Author
- Abbaneo D
- Abbiendi G
- Abbrescia M
- Abdullin S
- Acosta D
- Acosta JG
- Acosta MV
- Adair A
- Adam N
- Adam W
- Adams MR
- Adams T
- Adiguzel A
- Adler V
- Adzic P
- Agostino L
- Agram JL
- Aguilar-Benitez M
- Aguilo E
- Ahmad M
- Ahmad WH
- Ahuja S
- Akchurin N
- Akgun B
- Akgun U
- Akin IV
- Alagoz E
- Albajar C
- Albayrak EA
- Albergo S
- Albrow M
- Alda Junior WL
- Alexander J
- Aliev T
- Almeida N
- Alver B
- Alverson G
- Alves GA
- Amapane N
- Amsler C
- Anagnostou G
- Anastassov A
- Anderson J
- Anderson M
- Andrea J
- Andreev V
- Andreev V
- Andreev Y
- Andrews W
- Anghel IM
- Anjos TS
- Antonelli L
- Antunes JR
- Antunovic Z
- Apanasevich L
- Apollinari G
- Appelt E
- Apresyan A
- Aranyi A
- Arce P
- Arcidiacono R
- Arenton MW
- Arfaei H
- Argiro S
- Arisaka K
- Arneodo M
- Arora S
- Asawatangtrakuldee C
- Asghar MI
- Askew A
- Assran Y
- Ata M
- Atac M
- Atramentov O
- Attikis A
- Auffray E
- Autermann C
- Auzinger G
- Avdeeva E
- Avery P
- Avetisyan A
- Azarkin M
- Azhgirey I
- Aziz T
- Azzi P
- Azzolini V
- Azzurri P
- Baarmand MM
- Babb J
- Bacchetta N
- Bachtis M
- Baden A
- Baeni L
- Baesso P
- Baffioni S
- Bagliesi G
- Bai Y
- Baillon P
- Bainbridge R
- Bakhshiansohi H
- Bakirci MN
- Bakken JA
- Balazs M
- Ball AH
- Ball G
- Ban Y
- Banerjee S
- Banerjee S
- Bansal S
- Banzuzi K
- Barbagli G
- Barberis E
- Barbone L
- Bardak C
- Barfuss AF
- Bargassa P
- Barge D
- Baringer P
- Barker A
- Barnes VE
- Barnett BA
- Barney D
- Barone L
- Barrett M
- Bartalini P
- Barth C
- Basegmez S
- Basso L
- Battilana C
- Baty C
- Bauer G
- Bauerdick LAT
- Baumgartel D
- Baur U
- Bayshev I
- Bazterra VE
- Bean A
- Beauceron S
- Beaudette F
- Beaupere N
- Bedjidian M
- Beernaert K
- Behrenhoff W
- Behrens U
- Belforte S
- Beliy N
- Belknap D
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- Bell KW
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- Bellinger JN
- Belotelov I
- Belyaev A
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- Bendavid J
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- Benvenuti AC
- Beranek S
- Beretvas A
- Bergauer T
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- Bergholz M
- Beri SB
- Bernardes CA
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- Betchart B
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- Bhat PC
- Bhatnagar V
- Bhattacharya S
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- Bilei GM
- Bilin B
- Bilinskas MJ
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- Blekman F
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- CMS Collaboration
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- Cutajar M
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- D'Agnolo RT
- D'Alessandro R
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- D'Enterria D
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- Da Costa EM
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- Damiao DD
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- Zheng Y
- Zhokin A
- Zhu B
- Zhu RY
- Zhukov V
- Zhukova V
- Ziebarth EB
- Ziegler J
- Zielinski M
- Zito G
- Zoeller MH
- Zotto P
- Zou W
- Zumerle G
- Zuranski A
- Publication venue
- 'IOP Publishing'
- Publication date
- 01/01/2012
- Field of study
The performance of muon reconstruction, identification, and triggering in CMS
has been studied using 40 inverse picobarns of data collected in pp collisions
at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection
criteria covering a wide range of physics analysis needs have been examined.
For all considered selections, the efficiency to reconstruct and identify a
muon with a transverse momentum pT larger than a few GeV is above 95% over the
whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4,
while the probability to misidentify a hadron as a muon is well below 1%. The
efficiency to trigger on single muons with pT above a few GeV is higher than
90% over the full eta range, and typically substantially better. The overall
momentum scale is measured to a precision of 0.2% with muons from Z decays. The
transverse momentum resolution varies from 1% to 6% depending on pseudorapidity
for muons with pT below 100 GeV and, using cosmic rays, it is shown to be
better than 10% in the central region up to pT = 1 TeV. Observed distributions
of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV
- Author
- Abbaneo D
- Abbiendi G
- Abbrescia M
- Abdullin S
- Acosta D
- Acosta JG
- Acosta MV
- Adair A
- Adam N
- Adam W
- Adams MR
- Adams T
- Adiguzel A
- Adler V
- Adzic P
- Agostino L
- Agram JL
- Aguilar-Benitez M
- Aguilo E
- Ahmad M
- Ahmad WH
- Ahuja S
- Akchurin N
- Akgun B
- Akgun U
- Akin IV
- Alagoz E
- Albajar C
- Albayrak EA
- Albergo S
- Albrow M
- Alda Junior WL
- Alexander J
- Aliev T
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- Alver B
- Alverson G
- Alves GA
- Amapane N
- Amsler C
- Anagnostou G
- Anastassov A
- Anderson J
- Anderson M
- Andrea J
- Andreev V
- Andreev V
- Andreev Y
- Andrews W
- Anghel IM
- Anjos TS
- Antonelli L
- Antunes JR
- Antunovic Z
- Apanasevich L
- Apollinari G
- Appelt E
- Apresyan A
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- Cockerill DJA
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- Wissing C
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- Wood JS
- Worm SD
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- Wyslouch B
- Xiao H
- Xie S
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- Yelton J
- Yetkin T
- Yi K
- Yildirim E
- Yilmaz Y
- Yohay R
- Yoo HD
- Yoo J
- Yoon AS
- York A
- Yu I
- Yu SS
- Yumiceva F
- Yun JC
- Zabel J
- Zabi A
- Zablocki J
- Zaganidis N
- Zakaria M
- Zalewski P
- Zanetti M
- Zang J
- Zang SL
- Zarubin A
- Zatserklyaniy A
- Zeinali M
- Zeise M
- Zeuner WD
- Zeyrek M
- Zhang J
- Zhang Z
- Zheng Y
- Zhokin A
- Zhu B
- Zhu RY
- Zhukov V
- Zhukova V
- Ziebarth EB
- Ziegler J
- Zielinski M
- Zito G
- Zoeller MH
- Zotto P
- Zou W
- Zumerle G
- Zuranski A
- Publication venue
- 'IOP Publishing'
- Publication date
- 01/01/2012
- Field of study
The performance of muon reconstruction, identification, and triggering in CMS
has been studied using 40 inverse picobarns of data collected in pp collisions
at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection
criteria covering a wide range of physics analysis needs have been examined.
For all considered selections, the efficiency to reconstruct and identify a
muon with a transverse momentum pT larger than a few GeV is above 95% over the
whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4,
while the probability to misidentify a hadron as a muon is well below 1%. The
efficiency to trigger on single muons with pT above a few GeV is higher than
90% over the full eta range, and typically substantially better. The overall
momentum scale is measured to a precision of 0.2% with muons from Z decays. The
transverse momentum resolution varies from 1% to 6% depending on pseudorapidity
for muons with pT below 100 GeV and, using cosmic rays, it is shown to be
better than 10% in the central region up to pT = 1 TeV. Observed distributions
of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV
- Author
- Abbaneo D
- Abbiendi G
- Abbrescia M
- Abdullin S
- Abdulsalam A
- Acosta D
- Acosta JG
- Acosta MV
- Adair A
- Adam N
- Adam W
- Adams MR
- Adams T
- Adiguzel A
- Adler V
- Adzic P
- Afanasiev S
- Agostino L
- Agram JL
- Aguilar-Benitez M
- Aguilo E
- Ahmad M
- Ahmad WH
- Ahuja S
- Akchurin N
- Akgun B
- Akgun U
- Akin IV
- Alagoz E
- Albajar C
- Albayrak EA
- Albergo S
- Albrow M
- Alcaraz Maestre J
- Alda Junior WL
- Alexander J
- Aliev T
- Alimena J
- Almeida N
- Alverson G
- Alves GA
- Amapane N
- Amsler C
- Anagnostou G
- Anastassov A
- Anderson J
- Anderson M
- Andrea J
- Andreev V
- Andreev V
- Andreev Y
- Andrews W
- Anghel IM
- Anjos TS
- Antonelli L
- Antunovic Z
- Apanasevich L
- Appelt E
- Apresyan A
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- Wyslouch B
- Xiao H
- Xie S
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- Yang M
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- Yazgan E
- Yelton J
- Yetkin T
- Yi K
- Yildirim E
- Yilmaz Y
- Yohay R
- Yoo HD
- Yoo J
- Yoon AS
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- Yu I
- Yu SS
- Yumiceva F
- Yun JC
- Zabel J
- Zabi A
- Zablocki J
- Zaganidis N
- Zakaria M
- Zalewski P
- Zanetti M
- Zang J
- Zarubin A
- Zatserklyaniy A
- Zeinali M
- Zeise M
- Zeuner WD
- Zeyrek M
- Zhang J
- Zhang Z
- Zheng Y
- Zhokin A
- Zhu B
- Zhu RY
- Zhukov V
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- Ziebarth EB
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- Zumerle G
- Zuranski A
- Publication venue
- 'American Physical Society (APS)'
- Publication date
- 01/01/2012
- Field of study
The azimuthal anisotropy of charged particles in PbPb collisions at
nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS
detector at the LHC over an extended transverse momentum (pt) range up to
approximately 60 GeV. The data cover both the low-pt region associated with
hydrodynamic flow phenomena and the high-pt region where the anisotropies may
reflect the path-length dependence of parton energy loss in the created medium.
The anisotropy parameter (v2) of the particles is extracted by correlating
charged tracks with respect to the event-plane reconstructed by using the
energy deposited in forward-angle calorimeters. For the six bins of collision
centrality studied, spanning the range of 0-60% most-central events, the
observed v2 values are found to first increase with pt, reaching a maximum
around pt = 3 GeV, and then to gradually decrease to almost zero, with the
decline persisting up to at least pt = 40 GeV over the full centrality range
measured.Comment: Replaced with published version. Added journal reference and DO
Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy
- Author
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- Abbiendi G
- Abbrescia M
- Abdullin S
- Abdulsalam A
- Acosta D
- Acosta JG
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- Adiguzel A
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- Akin IV
- Alagoz E
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- Aldaya Martin M
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- Yilmaz Y
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- Zielinski M
- Zito G
- Zou W
- Zucchetta A
- Zumerle G
- Zuranski A
- Publication venue
- 'American Physical Society (APS)'
- Publication date
- 01/01/2012
- Field of study
A search for new physics is performed in events with two same-sign isolated
leptons, hadronic jets, and missing transverse energy in the final state. The
analysis is based on a data sample corresponding to an integrated luminosity of
4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of
7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of
140 increase in integrated luminosity over previously published results. The
observed yields agree with the standard model predictions and thus no evidence
for new physics is found. The observations are used to set upper limits on
possible new physics contributions and to constrain supersymmetric models. To
facilitate the interpretation of the data in a broader range of new physics
scenarios, information on the event selection, detector response, and
efficiencies is provided.Comment: Published in Physical Review Letter
Compressed representation of a partially defined integer function over multiple arguments
- Author
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- Abbiendi G
- Abbrescia M
- Abdelalim AA
- Abdullin S
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- Christiansen T
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- Cimmino A
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- Cittolin S
- Ciulli V
- Civinini C
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- Cline D
- CMS Collaboration
- Coarasa Perez JA
- Cockerill DJA
- Colafranceschi S
- Colaleo A
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- Contardo D
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- Costantini S
- Costanza F
- Couderc F
- Coughlan JA
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- Cremaldi LM
- Cripps N
- Cuevas J
- Cuffiani M
- Cumalat JP
- Cussans D
- Custodio A
- Cutajar M
- Cutts D
- Cwiok M
- Czellar S
- D'Agnolo RT
- D'Alessandro R
- D'Alfonso M
- d'Enterria D
- D'Hondt J
- Da Costa EM
- Dabrowski A
- Daci N
- Dahmes B
- Dahms T
- Dalchenko M
- Dallavalle GM
- Damgov J
- Danielson T
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- Daskalakis G
- Dasu S
- Daubie E
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- de Barbaro P
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- de Cassagnac RG
- De Cosa A
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- Publication venue
- Publication date
- 01/01/2013
- Field of study
In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one
Measurement of jet fragmentation into charged particles in pp and PbPb collisions at sqrt(s[NN]) = 2.76 TeV
- Author
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- Stuart D
- Sturdy J
- Suarez I
- Suarez RG
- Sudano E
- Sudhakar K
- Sulak L
- Sulimov V
- Sultanov G
- Sumorok K
- Sumowidagdo S
- Sun W
- Sung K
- Surat UE
- Svintradze I
- Svyatkovskiy A
- Swanson J
- Swartz M
- Symonds P
- Szillasi Z
- Szleper M
- Sznajder A
- Tadel M
- Takahashi M
- Tali B
- Tambe N
- Tan P
- Tao J
- Tapper A
- Taroni S
- Tatarinov A
- Taurok A
- Tauscher L
- Taylor L
- Tcholakov V
- Temple J
- Tenchini R
- Teng H
- Teo WD
- Teodorescu L
- Teyssier D
- Thea A
- Theofilatos K
- Thom J
- Thomas L
- Thomas S
- Thompson J
- Thomsen J
- Thyssen F
- Tiko A
- Timciuc V
- Tinti G
- Tiras E
- Titov M
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- Toback D
- Tomalin IR
- Tonelli G
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- Tonwar SC
- Topakli H
- Topaksu AK
- Torassa E
- Toropin A
- Torre P
- Tosi M
- Tosi S
- Tourtchanovitch L
- Traczyk P
- Tran NV
- Travaglini R
- Trayanov R
- Treille D
- Tricomi A
- Tripathi M
- Trocino D
- Trocsanyi ZL
- Troendle D
- Tropiano A
- Troshin S
- Tsamalaidze Z
- Tsang KV
- Tschudi Y
- Tsirou A
- Tu Y
- Tucker J
- Tully C
- Tumasyan A
- Tuo S
- Tuominen E
- Tuominiemi J
- Tuovinen E
- Tupputi S
- Turkewitz J
- Turner M
- Tuuva T
- Tuve C
- Twedt E
- Tytgat M
- Tyurin N
- Tzeng YM
- Ujvari B
- Ulmer KA
- Ulrich R
- Ungaro D
- Uplegger L
- Urscheler C
- Uvarov L
- Uzunian A
- Vaandering EW
- Valls N
- Valuev V
- Van Doninck W
- Van Haevermaet H
- Van Hove P
- Van Mechelen P
- Van Mulders P
- Van Onsem GP
- Van Remortel N
- Van Spilbeeck A
- Vander Velde C
- Vanelderen L
- Vanini S
- Vanlaer P
- Vardanyan I
- Varela J
- Varelas N
- Vargas JER
- Vartak A
- Vaughan J
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- Vazquez Valencia F
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- Veeraraghavan V
- Velasco M
- Velicanu D
- Velkovska J
- Venditti R
- Venturi A
- Verdier P
- Verdini PG
- Veres GI
- Vergili LN
- Vergili M
- Verwilligen P
- Verzetti M
- Veszpremi V
- Vesztergombi G
- Veverka J
- Vidal R
- Vila I
- Vilar Cortabitarte R
- Villasenor-Cendejas LM
- Villella I
- Vinogradov A
- Virdee T
- Viret S
- Vischia P
- Vishnevskiy D
- Vitulo P
- Vlasov E
- Vlimant JR
- Vodopiyanov I
- Vogel H
- Volkov A
- Volobouev I
- Volodko A
- Volpe R
- Vorobiev I
- Vorobyev A
- Vorobyev A
- Voutilainen M
- Vuosalo C
- Vutova M
- Wagner P
- Wagner SR
- Wagner-Kuhr J
- Wakefield S
- Wallny R
- Walsh R
- Walsh S
- Waltenberger W
- Walzel G
- Wan X
- Wang J
- Wang J
- Wang M
- Wang S
- Wang X
- Wang Z
- Wardle N
- Wasserbaech S
- Wayand S
- Wayne M
- Weber H
- Weber HA
- Weber M
- Weber M
- Wehrli L
- Weiler T
- Weinberg M
- Wendland L
- Weng Y
- Wenger EA
- Werner JS
- West C
- Wetzel J
- Whitbeck A
- Whitmore J
- Whyntie T
- Wickramage N
- Widl E
- Wilken R
- Wilkinson R
- Williams G
- Williams T
- Willmott C
- Wimpenny S
- Winer BL
- Winn D
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- Wissing C
- Wittich P
- Wittmer B
- Woehri HK
- Wolf M
- Wolf R
- Womersley WJ
- Won S
- Wood D
- Wood J
- Wood JS
- Worm SD
- Wright D
- Wrochna G
- Wu W
- Wuerthwein F
- Wulz C-E
- Wyslouch B
- Xiao H
- Xie S
- Xu M
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- Yang F
- Yang M
- Yang Y
- Yang ZC
- Yazgan E
- Yelton J
- Yetkin T
- Yi K
- Yildirim E
- Yilmaz Y
- Yohay R
- Yoo HD
- Yoo J
- Yoon AS
- York A
- Yu I
- Yu SS
- Yumiceva F
- Yun JC
- Zabel J
- Zabi A
- Zablocki J
- Zaganidis N
- Zakaria M
- Zalewski P
- Zanetti M
- Zang J
- Zarubin A
- Zatserklyaniy A
- Zeinali M
- Zeise M
- Zeuner WD
- Zeyrek M
- Zhang J
- Zhang Z
- Zheng Y
- Zhokin A
- Zhu B
- Zhu RY
- Zhukov V
- Zhukova V
- Zielinski M
- Zito G
- Zotto P
- Zou W
- Zucchetta A
- Zumerle G
- Zuranski A
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2012
- Field of study
Jet fragmentation in pp and PbPb collisions at a centre-of-mass energy of
2.76 TeV per nucleon pair was studied using data collected with the CMS
detector at the LHC. Fragmentation functions are constructed using
charged-particle tracks with transverse momenta pt > 4 GeV for dijet events
with a leading jet of pt > 100 GeV. The fragmentation functions in PbPb events
are compared to those in pp data as a function of collision centrality, as well
as dijet-pt imbalance. Special emphasis is placed on the most central PbPb
events including dijets with unbalanced momentum, indicative of energy loss of
the hard scattered parent partons. The fragmentation patterns for both the
leading and subleading jets in PbPb collisions agree with those seen in pp data
at 2.76 TeV. The results provide evidence that, despite the large parton energy
loss observed in PbPb collisions, the partition of the remaining momentum
within the jet cone into high-pt particles is not strongly modified in
comparison to that observed for jets in vacuum.Comment: Submitted to the Journal of High Energy Physic
Recruitment of a SAP18-HDAC1 Complex into HIV-1 Virions and Its Requirement for Viral Replication
- Author
- A Cereseto
- A Engleman
- A Klochendler-Yeivin
- A Morozov
- A Pumfery
- AL Brass
- C Hildmann
- C Treand
- CA Hassig
- CJ Guidi
- CW Roberts
- CW Roberts
- David Ott
- DE Ott
- E Agbottah
- E Yung
- E Yung
- EA Hehl
- EM Poeschla
- G Jiang
- Ganjam V. Kalpana
- GV Kalpana
- H Hanawa
- H Kato
- I Versteege
- J Ahringer
- J Chai
- JA Martens
- Jennifer Cano
- K Zhu
- Kelvin P. Davies
- M Cavrois
- M Llano
- M Maroun
- M Sorin
- M Sorin
- M Stevens
- M Stremlau
- M Topper
- Masha Sorin
- MH Kuo
- ML Phelan
- NJ Moorman
- P Cherepanov
- S Iordanskiy
- S Sif
- S-WG Cheng
- S.-W. Grace Cheng
- Sheeba Mathew
- Supratik Das
- T Mahmoudi
- Thomas J. Hope
- V Quivy
- VD Dang
- W Wang
- X Wu
- Xuanling Shi
- Xuhong Wu
- Y Ariumi
- ZK Zhang
- Publication venue
- Public Library of Science
- Publication date
- 01/06/2009
- Field of study
HIV-1 integrase (IN) is a virally encoded protein required for integration of viral cDNA into host chromosomes. INI1/hSNF5 is a component of the SWI/SNF complex that interacts with HIV-1 IN, is selectively incorporated into HIV-1 (but not other retroviral) virions, and modulates multiple steps, including particle production and infectivity. To gain further insight into the role of INI1 in HIV-1 replication, we screened for INI1-interacting proteins using the yeast two-hybrid system. We found that SAP18 (Sin3a associated protein 18 kD), a component of the Sin3a-HDAC1 complex, directly binds to INI1 in yeast, in vitro and in vivo. Interestingly, we found that IN also binds to SAP18 in vitro and in vivo. SAP18 and components of a Sin3A-HDAC1 complex were specifically incorporated into HIV-1 (but not SIV and HTLV-1) virions in an HIV-1 IN–dependent manner. Using a fluorescence-based assay, we found that HIV-1 (but not SIV) virion preparations harbour significant deacetylase activity, indicating the specific recruitment of catalytically active HDAC into the virions. To determine the requirement of virion-associated HDAC1 to HIV-1 replication, an inactive, transdominant negative mutant of HDAC1 (HDAC1H141A) was utilized. Incorporation of HDAC1H141A decreased the virion-associated histone deacetylase activity. Furthermore, incorporation of HDAC1H141A decreased the infectivity of HIV-1 (but not SIV) virions. The block in infectivity due to virion-associated HDAC1H141A occurred specifically at the early reverse transcription stage, while entry of the virions was unaffected. RNA-interference mediated knock-down of HDAC1 in producer cells resulted in decreased virion-associated HDAC1 activity and a reduction in infectivity of these virions. These studies indicate that HIV-1 IN and INI1/hSNF5 bind SAP18 and selectively recruit components of Sin3a-HDAC1 complex into HIV-1 virions. Furthermore, HIV-1 virion-associated HDAC1 is required for efficient early post-entry events, indicating a novel role for HDAC1 during HIV-1 replication
Analysis of the Expression, Secretion and Translocation of the Salmonella enterica Type III Secretion System Effector SteA
- Author
- A Subtil
- A Subtil
- AJ Baumler
- B Coburn
- B Misselwitz
- BD Jones
- BH Kim
- BK Coombes
- BK Coombes
- CA Lee
- CB García-Calderón
- CD Ellermeier
- CK Schmitt
- CM Collazo
- D Drecktrah
- D Hanahan
- D Wang
- Dipshikha Chakravortty
- EA Miao
- EA Miao
- EJ McGhie
- Elena Cardenal-Muñoz
- F Van Immerseel
- F Van Immerseel
- Francisco Ramos-Morales
- GR Cornelis
- GS Niemann
- H Gong
- H Russmann
- H Schmieger
- I Gantois
- I Hautefort
- J Bernal-Bayard
- J Bernal-Bayard
- J Bispham
- J Deiwick
- JA Crawford
- JA Ibarra
- JA Sorg
- JE Deane
- JH Cummings
- JH Miller
- K Geddes
- KA Datsenko
- KA Fields
- KA Walker
- KE Riordan
- KH Darwin
- KH Darwin
- KL Penheiter
- L Hedegaard
- L Valinsky
- LC Brawn
- LD Hernandez
- LM Schechter
- M Lara-Tejero
- M Lara-Tejero
- M Lower
- M Mavris
- M Mavris
- MA Jones
- MH Karavolos
- MP Sory
- NF Brown
- P Ghosh
- P Glaser
- P Malik-Kale
- P Mazurkiewicz
- PJ Edqvist
- PP Cherepanov
- R Arnold
- R Samudrala
- RK Chan
- RM Tsolis
- S Uzzau
- SA Lloyd
- SA Lloyd
- SB Van Engelenburg
- SE Osborne
- SH Lee
- SL Fink
- SR Maloy
- T Kubori
- T Le Gall
- T Ren
- TD Lawley
- V Bajaj
- V Kuhle
- XJ Yu
- Y Wang
- Y Yang
- YH Sun
- Publication venue
- Public Library of Science
- Publication date
- 01/01/2011
- Field of study
Many Gram-negative pathogens possess virulence-related type III secretion systems. Salmonella enterica uses two of these systems, encoded on the pathogenicity islands SPI-1 and SPI-2, respectively, to translocate more than 30 effector proteins into eukaryotic host cells. SteA is one of the few effectors that can be translocated by both systems. We investigated the conditions affecting the synthesis of this effector, its secretion to culture media and its translocation into host cells. Whereas steA was expressed under a wide range of conditions, some factors, including low and high osmolarity, and presence of butyrate, decreased expression. SteA was efficiently secreted to the culture media under both SPI-1 and SPI-2 inducing conditions. The kinetics of translocation into murine macrophages and human epithelial cells was studied using fusions with the 3xFLAG tag, and fusions with CyaA from Bordetella pertussis. Translocation into macrophages under non-invasive conditions was mainly dependent on the SPI-2-encoded type III secretion system but some participation of the SPI-1 system was also detected 6 hours post-infection. Interestingly, both type III secretion systems had a relevant role in the translocation of SteA into epithelial cells. Finally, a deletion approach allowed the identification of the N-terminal signal necessary for translocation of this effector. The amino acid residues 1–10 were sufficient to direct translocation into host cells through both type III secretion systems. Our results provide new examples of functional overlapping between the two type III secretion systems of Salmonella
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