4 research outputs found
Insights into the mechanism of Apoptin's exquisitely selective anti-tumor action from atomic level characterization of its conformation and dynamics
- Author
- Publication venue
- 'Elsevier BV'
- Publication date
- 20/03/2018
- Field of study
Apoptin is a 121 residue protein which forms large, soluble aggregates and possesses an exceptionally selectively cytotoxic action on cancer cells. In the accompanying paper, we described the design, production and initial characterization of an Apoptin truncated variant called H-ApopΔProΔLeu. Whereas both the variant and wild type protein possess similar selective cytotoxicity against cancer cells following transfection, only the variant is cytotoxic when added externally. Remarkably, as observed by gel filtration chromatography and dynamic light scattering, H-ApopΔProΔLeu lacks the tendency of wild type Apoptin to form large aggregates, which greatly facilitated the study of its biological properties. Here, we characterize the conformation and dynamics of H-ApopΔProΔLeu. Using a battery of 2D, 3D and (4,2)D NMR spectra, the essentially complete H, C and N resonance assignments of H-ApopΔProΔLeu were obtained. The analysis of these data shows that the variant is an intrinsically disordered protein, which lacks a preferred conformation. This conclusion is corroborated by a lack of protection against proteolytic cleavage and hydrogen/deuterium exchange. Moreover, the CD spectra are dominated by random coil contributions. Finally, H-N NOE ratios are low, which indicates flexibility on the ps-ns time scale. Interestingly, H-ApopΔProΔLeu's intrinsically disordered ensemble is not significantly altered by the redox state of its Cys residues or by Thr phosphorylation, which has been proposed to play a key role in Apoptin's selective cytotoxicity. These results serve to better comprehend Apoptin's remarkably selective anticancer action and provide a framework for the future design of improved Apoptin variants.Peer Reviewe
Tromboembolia pulmonar. Luces y sombras
- Author
- Publication venue
- 'Elsevier BV'
- Publication date
- Field of study
Pulmonary Thromboembolism. Light and Shadows
- Author
- Publication venue
- 'Elsevier BV'
- Publication date
- Field of study
Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data
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- Paul J Nederkoorn
- Paul L.M. de Kort
- Pauline Renou
- Paut Greebe
- Peter J Mitchell
- Peter J Mitchell
- Peter J. Koudstaal
- Philip White
- Philip White
- Philippe Graveleau
- Pierre Aguettaz
- Pierre Bounolleau
- Pierre Clavelou
- Pierre Garnier
- Pierre Guedin
- Pierre Guedin
- Pierre-Alexandre Baillot
- PK Stys
- Poh Sien Loh
- Puck SS Fransen
- Purushotham
- Q Shah
- R Agid
- R Bartt
- R Bellon
- R Brant
- R Budzik
- R Carandang
- R Cerejo
- R Chan
- R Collins
- R Dahlgren
- R Dharia
- R Doyle
- R du Mesnil de Rochemont
- R Farb
- R Gandhi
- R GarcĂa-Sort
- R Goddeau
- R Jahan
- R Martin
- R Moftakhar
- R Navarro
- R Pafford
- R Pratt
- R Priest
- R Reddy
- R Roberts
- R Sawyer
- R Shamloul
- R Swartz
- R Taylor
- R Tummala
- R Turner
- R van Dijk
- R Vandorpe
- R Whelan
- R Wiegner
- RA Ashforth
- RA Willinsky
- RA Willinsky
- Rachael McCoy
- Ralph Geuskens
- Raphael Blanc
- Raphael Le Bouc
- Raul G. Nogueira
- Raul Mariano Musacchio
- Raymie-Jayce Ganpat
- RD Ecker
- Rebecca Scroop
- Rekha Keshvara
- Renan Sales Barros
- Renske M. van den Berg-Vos
- René Anxionnat
- René J. Dallinga
- René van den Berg
- Reza Jahan
- Reza Jahan
- Richard Chiacchierini
- Richard Dowling
- Richard Macdonnell
- Richard Perry
- Richard Stark
- Rita Ghatala
- RJ Owen
- Rob H Lo
- Rob Lenthall
- Robert J van Oostenbrugge
- Robert J. van Oostenbrugge
- Roberto Riva
- Roel J.J. Heijboer
- Roeland Dobbe
- Ronil V Chandra
- RĂ©my Beaujeux
- RĂĽdiger von Kummer
- S Adatia
- S Al-Boutros
- S Amaro
- S Arkin
- S Barnwell
- S Biethahn
- S Blayney
- S Boned
- S Boo
- S Bracard
- S Crandall
- S Crann
- S Dancer
- S Decesare
- S Dehkharghani
- S Dharmadhikari
- S Doppelheuer
- S Duff
- S Faro
- S Gallagher
- S Gelabert
- S Guggenberger
- S Göricke
- S Hall
- S Hasan
- S Hou
- S Jamieson
- S John
- S Karabegovich
- S Koch
- S Krieter
- S Lacusta
- S Lanthier
- S Lee
- S Lescher
- S Looby
- S Lownie
- S Man
- S Mishra
- S Murphy
- S Murphy
- S O'Leary
- S Onteddu
- S Ozark
- S Patel
- S Patil
- S Perez
- S Phillips
- S Prothmann
- S Quarfordt
- S Quarfordt
- S Rangaraju
- S Remollo
- S Renfrow
- S Rho
- S Robert
- S Rohde
- S Rudilosso
- S Ryoo
- S Sheth
- S Shine
- S Smyth
- S Starkman
- S Streib
- S Subramaniam
- S Tateshima
- S Taudorf
- S Wunderlich
- S Zaidi
- S-I Sohn
- Sabrina Debruxelles
- Sal Lamin
- Sandra Felix
- Sandrine Deltour
- Sandrine Wiertlewski
- Sanjeev Nayak
- Sarah Evain
- Saver
- Saver
- SB Coutts
- Scott Brown
- Scott Hamilton
- Sebastiaan F. de Bruijn
- Serge Bakchine
- Serge Bracard
- Serge Evrard
- Servane Mouton
- Sherisse Celestino
- Silvan Licher
- Silvia Pistocchi
- Simon Salinas
- SJ Kim
- SJ You
- Sjoerd F.M. Jenniskens
- Skye Coote
- Solène De Gaalon
- Sophie Crozier
- Sophie Godard Ducceschi
- SR Belagaje
- SS Naik
- Stefan Vinken
- Stefanie Schipperen
- Steff Lewis
- Stephane Velasco
- Stephen M Davis
- Stephen M Davis
- Susan Day
- Sylvain Lachaud
- Sylvie Godon-Hardy
- SĂ©bastien Richard
- SĂ©bastien Richard
- SĂ©verine Debiais
- T Boeckh-Behrens
- T Coughlan
- T Daly
- T Daly
- T Davis
- T Devlin
- T Devlin
- T Galvin
- T Harbo
- T Hendrickson
- T Hyldal
- T Jeerakathil
- T Kahles
- T Krings
- T Larson
- T Lowenkopf
- T Lynch
- T Marotta
- T Meindl
- T Musuka
- T Nguyen
- T Reiff
- T Roberts
- T Sajobi
- T Sajobi
- T Scheibe-Mirek
- T Stavngaard
- T Stewart
- T Stewart
- T Stewart
- T Walsh
- TA Yeo
- Tae-Hee Cho
- Tanya Frost
- TB Kotylak
- Teddy Y Wu
- TG Jovin
- Thanh Phan
- Theo Stijnen
- Thibaud Lebouvier
- Thierry Moulin
- Thomas J Oxley
- Thomas Liebig
- Thomas Ritzenthaler
- Thomas Ronziere
- Thompson Robinson
- Tiemen van Boxtel
- Timo Krings
- Timothy Ang
- Timothy J Harrington
- Timothy J Kleinig
- Tiphaine Rouaud
- Tissa Wijeratne
- Tobien H.C.M.L. Schreuder
- Tommy Andersson
- Tony Goddard
- TS Field
- Tudor G Jovin
- Tudor G. Jovin
- TW Watson
- U Grzyska
- V Biberacher
- V Chang
- V Costalat
- V Deshmukh
- V Dubuc
- V Kalugdan
- V Nambiar
- V Obach
- V Pandey
- V Patel
- V Reddy
- V Snyder
- V Szeder
- V Totoraitis
- V Totoraitis
- V Yang
- V Zegarac
- VA Coté
- Valérie Domigo
- Valérie Wolff
- Vasdev Ashok
- Vincent Cahagne
- Vincent Costalat
- Vincent Guiraud
- Violaine Rouaud Jaffrenou
- Vitor Mendes Pereira
- VK Reddy
- W Clark
- W Holloway
- W Maloney
- W Montanera
- W Morgan
- W Pfeilschifer
- W Poon
- W Tekle
- Wade Smith
- Werner Hacke
- WF Morrish
- WF Morrish
- Willem Jan J. van Rooij
- Willy Struijk
- Wilma Pellikaan
- Wim H van Zwam
- Wim H. van Zwam
- Winston Chong
- Wintermark
- WJ Hicks
- WJ Montanera
- WJ Montanera
- Wouter J Schonewille
- X Ayrignac
- X Urra
- Xavier Barreau
- Xavier Ducrocq
- Xavier Leclerc
- Y Deschaintre
- Y Li
- Y Yu
- Yannick Bejot
- YD Kim
- Yince Loh
- Yves Chau
- Yves Samson
- Yvo B W E M Roos
- Yvo B.W.E.M. Roos
- Z El-Zammar
- Z Khawaja
- Zofia Ross
- Zoltan Szatmary
- Zwenneke Flach
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