Sequence similarity in structurally dissimilar proteins

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Prediction of a common structural scaffold for proteasome lid, COP9-signalosome and eIF3 complexes

BACKGROUND: The 'lid' subcomplex of the 26S proteasome and the COP9 signalosome (CSN complex) share a common architecture consisting of six subunits harbouring a so-called PCI domain (proteasome, CSN, eIF3) at their C-terminus, plus two subunits containing MPN domains (Mpr1/Pad1 N-terminal). The translation initiation complex eIF3 also contains PCI- and MPN-domain proteins, but seems to deviate from the 6+2 stoichiometry. Initially, the PCI domain was defined as the region of detectable sequence similarity between the components mentioned above. RESULTS: During an exhaustive bioinformatical analysis of proteasome components, we detected multiple instances of tetratrico-peptide repeats (TPR) in the N-terminal region of most PCI proteins, suggesting that their homology is not restricted to the PCI domain. We also detected a previously unrecognized PCI domain in the eIF3 component eIF3k, a protein whose 3D-structure has been determined recently. By using profile-guided alignment techniques, we show that the structural elements found in eIF3k are most likely conserved in all PCI proteins, resulting in a structural model for the canonical PCI domain. CONCLUSION: Our model predicts that the homology domain PCI is not a true domain in the structural sense but rather consists of two subdomains: a C-terminal 'winged helix' domain with a key role in PCI:PCI interaction, preceded by a helical repeat region. The TPR-like repeats detected in the N-terminal region of PCI proteins most likely form an uninterrupted extension of the repeats found within the PCI domain boundaries. This model allows an interpretation of several puzzling experimental results

The PROSITE database, its status in 1999

The PROSITE database (http://www.expasy.ch/sprot/prosite.html) consists of biologically significant patterns and profiles formulated in such a way that with appropriate computational tools it can help to determine to which known family of protein (if any) a new sequence belongs, or which known domain(s) it contain

On Entangled Multi-particle Systems in Bohmian Theory

Arguments are presented to show that in the case of entangled systems there are certain difficulties in implementing the usual Bohmian interpretation of the wave function in a straightforward manner. Specific examples are given.Comment: 7 page

Deformation behaviour of ion-irradiated FeCr : A nanoindentation study

Understanding the mechanisms of plasticity in structural steels is essential for the operation of next-generation fusion reactors. This work on the deformation behaviour of FeCr, focusses on distinguishing the nucleation of dislocations to initiate plasticity, from their propagation through the material. Fe3Cr, Fe5Cr, and Fel OCr were irradiated with 20 MeV Fe3+ ions at room temperature to doses of 0.008 dpa and 0.08 dpa. Nanoindentation was then carried out with Berkovich and spherical indenter tips. Our results show that the nucleation of dislocations is mainly from pre-existing sources, which are not significantly affected by the presence of irradiation defects or Cr%. Yield strength, an indicator of dislocation mobility, increases with irradiation damage and Cr content, while work hardening capacity decreases mainly due to irradiation defects. The synergistic effects of Cr and irradiation damage in FeCr appear to be more important for the propagation of dislocations than for their nucleation.Peer reviewe

PII: S0968-0004(01)01835-7

Research Update We anticipate that further experimental investigation of the specific role of each of the five classes of Brix domain proteins in eukaryote model organisms, especially in yeast, will yield valuable new insights about ribosome synthesis and be key to our understanding of the ribosome biogenesis pathway. Acknowledgements We are grateful to E. Bogengruber, M. Breitenbach, F.M. Jantsch and G. Lepperdinger for supplying experimental data on sequence and function of Brix (AF319877) and yol077c before publication and for extensive discussion of the Brix sequence analysis results. This research was supported by Boehringer-Ingelheim International. Ubiquitin is a small protein, highly conserved among eukaryotes, that becomes covalently attached to both itself and a variety of cellular proteins 1,2 . The role of this ubiquitination is mostly to target proteins to the 26S proteasome degradation pathway 3 . In some cases, monoubiquitination (e.g. of histones) does not lead to degradation, but instead regulates other cellular processes such as chromatin remodeling 4 . Recently, several reports have described a role for monoubiquitination in a different pathway of protein degradation -the endocytosis and subsequent proteolysis of receptors and other transmembrane proteins by the vacuole or the lysosome 5,6 . According to the current model, the decisions about which protein is to be degraded at a specific time is made by the ubiquitination machinery, often in response to a prior event such as phosphorylation. Consequently, both the proteasome and the endocytosis machinery need a mechanism by which to faithfully recognize ubiquitinated proteins. The 26S proteasome comprises two main particles: the 20S core proteasome and the 19S regulatory complex. Subunit S5a (also known as Rpn10) of the 19S regulator binds polyubiquitin chains and has a preference for chains containing four or more ubiquitin monomers. The ubiquitin-interacting region has been mapped to two short, related motifs that are found in all members of the S5a family 7 . Using these regions, which comprise ~20 residues, as a starting point, we searched for other potential ubiquitin-binding sequences. Specifically, we used a combination of iterative database searches with generalized profiles, and Hidden Markov Models (profile-HMMs) 8 . Only sequences that matched a profile or an HMM derived from previously established family members, with error probabilities of p < 0.01, were used for subsequent iteration cycles. After eight cycles, the sequence motif 4 Migeon, J.C. et al. (1999) converged to a set of proteins shown in An observation of particular interest is the occurrence of UIMs in four classes of proteins involved in receptor endocytosisthe Eps15 subfamily of EH-domain proteins, the epsin subfamily of ENTH-domain proteins and two families of VHS-domain proteins, including the FYVE-finger proteins HRS and Vps27, and the SH3-domain proteins STAM and HBP. Eps15 is phosphorylated on Tyr850 by the ligandactivated epidermal growth factor (EGF) receptor and this phosphorylation is required for subsequent receptor endocytosis 10 . Furthermore, Eps15 binds to epsin, and both of these proteins interact with components of the endocytosis machinery, including clathrin and the AP-2 complex 11,12 . The fact that the phosphorylation site of Eps15 is immediately adjacent to a tandem UIM suggests that this motif might be involved in the regulated endocytosis of the EGF receptor. Liquid facets (lqf), an epsin from Drosophila melanogaster, was identified in a genetic screen as a dominant enhancer of the fat facets (faf) mutant eye phenotype 13 . This relationship links the gene encoding lqf with the ubiquitin system because faf is a deubiquitinating enzyme. An additional link between Eps15 and ubiquitin recognition is provided by the yeast protein Ede1p, the closest homolog of mammalian Eps15 (Ref. 14): in the yeast protein, the UIM is replaced by a UBA domain, a homology domain known to bind ubiquitin 15 . Proteins with an N-terminal VHS domain can be divided into three subtypes on the basis of their domain organization: (1) Vps27-HRS-like (type A); (2) STAM-HBP-like (type B); and (3) other proteins (type C) (se

Novel Phosphonium-Based Ionic Liquid Electrolytes for Battery Applications

In this study, we address the fundamental question of the physicochemical and electrochemical properties of phosphonium-based ionic liquids containing the counter-ions bis(trifluoromethanesul fonyl)imide ([TFSI]−) and bis(fluorosulfonyl)imide ([FSI]−). To clarify these structure–property as well as structure–activity relationships, trimethyl-based alkyl- and ether-containing phosphonium ILs were systematically synthesized, and their properties, namely density, flow characteristics, alkali metal compatibility, oxidative stability, aluminum corrosivity as well as their use in Li-ion cells were examined comprehensively. The variable moiety on the phosphonium cation exhibited a chain length of four and five, respectively. The properties were discussed as a function of the side chain, counter-ion and salt addition ([Li][TFSI] or [Li][FSI]). High stability coupled with good flow characteristics were found for the phosphonium IL [P1114][TFSI] and the mixture [P1114][TFSI] + [Li][TFSI], respectively

Novel Phosphonium-Based Ionic Liquid Electrolytes for Battery Applications

In this study, we address the fundamental question of the physicochemical and electrochemical properties of phosphonium-based ionic liquids containing the counter-ions bis(trifluoromethanesul fonyl)imide ([TFSI]) and bis(fluorosulfonyl)imide ([FSI]). To clarify these structure–property as well as structure–activity relationships, trimethyl-based alkyl- and ether-containing phosphonium ILs were systematically synthesized, and their properties, namely density, flow characteristics, alkali metal compatibility, oxidative stability, aluminum corrosivity as well as their use in Li-ion cells were examined comprehensively. The variable moiety on the phosphonium cation exhibited a chain length of four and five, respectively. The properties were discussed as a function of the side chain, counter-ion and salt addition ([Li][TFSI] or [Li][FSI]). High stability coupled with good flow characteristics were found for the phosphonium IL [P1114][TFSI] and the mixture [P1114][TFSI] + [Li][TFSI], respectively

Structure-Property Relation of Trimethyl Ammonium Ionic Liquids for Battery Applications

Ionic liquids are attractive and safe electrolytes for diverse electrochemical applications such as advanced rechargeable batteries with high energy densities. Their properties that are beneficial for energy storage and conversion include negligible vapor-pressure, intrinsic conductivity as well as high stability. To explore the suitability of a series of ionic liquids with small ammonium cations for potential battery applications, we investigated their thermal and transport properties. We studied the influence of the symmetrical imide-type anions bis(trifluoromethanesulfonyl)imide ([TFSI]−) and bis(fluorosulfonyl)imide ([FSI]−), side chain length and functionalization, as well as lithium salt content on the properties of the electrolytes. Many of the samples are liquid at ambient temperature, but their solidification temperatures show disparate behavior. The transport properties showed clear trends: the dynamics are accelerated for samples with the [FSI]− anion, shorter side chains, ether functionalization and lower amounts of lithium salts. Detailed insight was obtained from the diffusion coefficients of the different ions in the electrolytes, which revealed the formation of aggregates of lithium cations coordinated by anions. The ionic liquid electrolytes exhibit sufficient stability in NMC/Li half-cells at elevated temperatures with small current rates without the need of additional liquid electrolytes, although Li-plating was observed. Electrolytes containing [TFSI]− anions showed superior stability compared to those with [FSI]− anions in battery tests