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Alexander V. Efimov
Deputy director, Institute of Protein Research, Russian Academy of Sciences
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Biochemistry. Biokhimii͡a 2010 Jan; 75(2)
A novel structural motif and structural trees for proteins containing it.
In the present study, a novel structural motif that can be represented as a combination of the known betaalphabeta-unit and psi-motif is described and analyzed. In theory, there are four possible combinations of the motifs since each of them can exis... expand abstractt in two forms, left-handed and right-handed. For this study, we have selected 140 nonhomologous proteins in which 158 combinations of such types have been found. The combination of the right-handed psi-motif and the right-handed betaalphabeta-unit has been shown to occur most often (87 cases out of 158) and the combination of the left-handed betaalphabeta-unit and the left-handed psi-motif does not occur at all. Three novel structural trees in which the commonly occurring combinations are taken as the root structures have been constructed. collapse abstract
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The Journal of general virology 2009 Nov; 90(Pt 12)
Domain organization of the N-terminal portion of hordeivirus movement protein TGBp1.
Three 'triple gene block' proteins known as TGBp1, TGBp2 and TGBp3 are required for cell-to-cell movement of plant viruses belonging to a number of genera including Hordeivirus. Hordeiviral TGBp1 interacts with viral genomic RNAs to form ribonucleopr... expand abstractotein (RNP) complexes competent for translocation between cells through plasmodesmata and over long distances via the phloem. Binding of hordeivirus TGBp1 to RNA involves two protein regions, the C-terminal NTPase/helicase domain and the N-terminal extension region. This study demonstrated that the extension region of hordeivirus TGBp1 consists of two structurally and functionally distinct domains called the N-terminal domain (NTD) and the internal domain (ID). In agreement with secondary structure predictions, analysis of circular dichroism spectra of the isolated NTD and ID demonstrated that the NTD represents a natively unfolded protein domain, whereas the ID has a pronounced secondary structure. Both the NTD and ID were able to bind ssRNA non-specifically. However, whilst the NTD interacted with ssRNA non-cooperatively, the ID bound ssRNA in a cooperative manner. Additionally, both domains bound dsRNA. The NTD and ID formed low-molecular-mass oligomers, whereas the ID also gave rise to high-molecular-mass complexes. The isolated ID was able to interact with both the NTD and the C-terminal NTPase/helicase domain in solution. These data demonstrate that the hordeivirus TGBp1 has three RNA-binding domains and that interaction between these structural units can provide a basis for remodelling of viral RNP complexes at different steps of cell-to-cell and long-distance transport of virus infection. collapse abstract
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Molekuliarnaia biologiia 43(3)
Novel structural tree for (alpha + beta)-proteins containing abCd-units
A database of 926 (alpha + beta)-proteins and (alpha + beta)-domains containing abCd-units (among them 401 are nonhomologous) has been compiled from the Protein Data Bank (total 2636 PDB entries). A novel structural tree for this structural class of ... expand abstractproteins that is composed of 286 possible polypeptide chain folds has been constructed. The structural classification of (alpha + beta)-proteins containing abCd-unit based on the structural tree has been developed. Both the database and the structural tree are accessible at the web-site (http://strees.protres.ru/). collapse abstract
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Biochemical and biophysical research communications 2009 Oct; 388(1)
Intramolecular triple helix as a model for regular polyribonucleotide (CAA)(n).
The regular (CAA)(n) polyribonucleotide, as well as the omega leader sequence containing (CAA)-rich core, have recently been shown to form cooperatively melted and compact structures. In this report, we propose a structural model for the (CAA)(n) seq... expand abstractuence in which the polyribonucleotide chain is folded upon itself, so that it forms an intramolecular triple helix. The triple helix is stabilized by hydrogen bonding between bases thus forming coplanar triads, and by stacking interactions between the base triads. A distinctive feature of the proposed triple helix is that it does not contain the canonical double-helix elements. The difference from the known triple helices is that Watson-Crick hydrogen bond pairings do not take place in the interactions between the bases within the base triads. collapse abstract
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Molekuliarnaia biologiia 42(2)
Novel structural tree for beta-proteins containing abcd-units
A database of 528 beta-proteins and beta-domains containing abcd-units (among them 244 are nonhomologous) has been compiled from the Protein Data Bank (total 1511 PDB entries). A novel structural tree for this structural class of proteins that is com... expand abstractposed of 153 possible polypeptide chain folds has been constructed. The structural classification of beta-proteins containing abcd-unit based on the structural tree has been developed. Both the database and the structural tree are accessible at the web-site (http://strees.protres.ru/). collapse abstract
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Molekuliarnaia biologiia 41(5)
Side-chain rotamers in protein alpha-alpha-hairpins and a mechanism of their selection
The observed features of side-chain rotamer distributions in protein alpha-alpha-hairpins are described. It was found that in left-turned alpha-alpha-hairpins most side chains occupying d-positions have t-rotamers and those in g-positions g- -rotamer... expand abstracts. In right-turned alpha-alpha-hairpins, most side chains in a-positions adopt g- -rotamers and those in e-positions t-rotamers. Analysis of these features enables us to conclude that selection of side-chain rotamers in alpha-alpha-hairpins depends on both the type of the alpha-helix packing and the residue position. The observed features can be explained taking into account the squeezing mechanism according to which interhelical interactions bring alpha-helices closer to each other and this effect squeezes side chains out of the helix-helix interface and as a result they adopt unique conformations. collapse abstract
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Biochemistry. Biokhimii͡a 2007 Dec; 73(1)
Structural trees for proteins containing phi-motifs.
In the present study, a novel structural motif of proteins referred to as the phi-motif is considered, and two novel structural trees in which the phi-motif is taken as the root structure have been constructed. The simplest phi-motif is formed by thr... expand abstractee adjacent beta-strands connected by loops and packed in one beta-sheet so that its overall fold resembles the Greek letter phi. Construction of the structural trees and modeling of folding pathways have shown that all structures of the protein superfamilies can be obtained by stepwise addition of alpha-helices and/or beta-strands to the root phi-motif taking into account a restricted set of rules inferred from known principles of protein structure. The structural trees are a good tool for structure comparison, structural classification of proteins, as well as for searching for all possible protein folds and folding pathways. collapse abstract
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Virology 2008 Mar; 373(1)
One more probable structural transition in potato virus X virions and a revised model of the virus coat protein structure.
We found that a 2-h incubation of potato virus X (PVX) virions in 10 mM Tris-HCl buffer pH 7.5 at -20 degrees C results in a strong but reversible drop in virion stability. Under these conditions, the PVX virions are completely disrupted by low (star... expand abstractting from 50 mM) concentrations of LiCl and CaCl(2) but not of NaCl. Incubation of PVX samples with 0.05-2 M LiCl at +4 degrees C did not result in virion disassembly and the virions were not disrupted upon incubation at -20 degrees C in 10 mM Tris-HCl buffer pH 7.5 without LiCl. We suggest that a 2-h incubation of the PVX virions at -20 degrees C in 10 mM Tris-HCl pH 7.5 results in a structural transition in the virus particles. A revised model of the three-dimensional organization of coat protein subunits in the PVX virions is proposed. This two-domain model explains better the high plasticity of the PVX CP structure. collapse abstract
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Molekuliarnaia biologiia 41(4)
Modified model of potato virus X coat protein structure
We propose the modified model of the structure of coat protein (CP) subunits in filamentous virions of potato virus X (PVX). The model is similar to the one proposed by us in 2001 for the CP of another helical plant virus (potato virus A) belonging t... expand abstracto other (potyvirus) group. In this model the PVX CP molecule consist of two main domains--a bundle of four alpha-helices located close to the virion long axis and a so-called RNP-fold (or abCd-fold) located near the virion surface. Basing on this model we suggest possible mechanism of described by J.G. Atabekov and colleagues structural transition ("remodeling") of the PVX virions resulting from their interaction with virus-specific TGB-1 protein. collapse abstract
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Molekuliarnaia biologiia 41(3)
Role of the structural context in selection of hydrophobic side-chain rotamers in a- and d-positions of alpha-helices
The study shows that in coiled-coil proteins the distribution of hydrophobic side-chain rotamers in a- and d-positions of alpha-helices is strongly dependent on the mutual arrangement of the a-helices. In coiled-coil dimers, where a-helices are packe... expand abstractd "face-to-face", most side chains occupying a-positions adopt t-rotamers, and those in d-positions adopt g- -rotamers. In tetramers, where alpha-helices are packed "side-by-side", most side chains in a-positions adopt g- -rotamers and those in d-positions adopt t-rotamers. These features can be used for prediction of side-chain rotamers in protein modeling and design. collapse abstract
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Biochemistry. Biokhimii͡a 2007 Jan; 72(2)
Mechanism of selection of side-chain rotamers in alpha-helices.
In this study, a possible mechanism of selection of side-chain rotamers based on the rotamer distributions in known coiled-coil proteins is suggested. According to this mechanism, interhelical hydrophobic, polar, and packing interactions bring alpha-... expand abstracthelices closer to each other and this effect squeezes side chains out of the helix-helix interface. As a result, in dimeric coiled coils and long alpha-alpha-hairpins where alpha-helices are packed in a face-to-face manner, most side chains occupying the a-positions have t-rotamers and those in the d-positions g(-)-rotamers. In tetramers, where alpha-helices are packed side-by-side, most side chains in the a-positions adopt g(-)-rotamers and those in the d-positions t-rotamers. collapse abstract
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Molekuliarnaia biologiia 39(5)
Analysis of interactions of buried polar side chains in beta-proteins
It was shown in qualitative and quantitative analyses of polar side chains inaccessible for water molecules as well as their interactions in 100 globular beta-structural proteins that completely buried polar side chains are widespread in beta-protein... expand abstracts, their vast majority being involved in "side chain-side chain" or "side chain-main chain" interactions. The analysis of the occurrence of different "side chain-partner" pairs permitted us to demonstrate that such interactions are selective. The results were compared with similar data obtained previously for alpha-helical proteins. collapse abstract
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Molekuliarnaia biologiia 38(5)
Investigation of helical plant virus ribonucleoprotein structures with the help of tritium planigraphy and theoretical modeling
The results of the studies of helical plant virus structures by tritium planigraphy (TP) method are discussed. TP method is based on bombardment of macromolecular objects with a stream of tritium atoms, followed by analysis of tritium label distribut... expand abstraction along the macromolecule. By combining the TP data with the results of theoretical predictions of the protein structure, it turned out to be possible to propose a model of the coat protein structure in the virions of potato virus X (the type member of potexvirus group) and potato virus A (one of the members of potyvirus group). With the help of TP it also managed to find subtle differences in the coat protein structure between wildtype tobacco mosaic virus (strain U1) and its mutant with two amino acid substitutions in the coat protein and alter host specificity. collapse abstract
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The Journal of biological chemistry 2005 Apr; 280(16)
pH-dependent substrate preference of pig heart lipoamide dehydrogenase varies with oligomeric state: response to mitochondrial matrix acidification.
Cycling of intracellular pH has recently been shown to play a critical role in ischemia-reperfusion injury. Ischemia-reperfusion also leads to mitochondrial matrix acidification and dysfunction. However, the mechanism by which matrix acidification co... expand abstractntributes to mitochondrial dysfunction, oxidative stress, and the resultant cellular injury has not been elucidated. We observe pH-dependent equilibria between monomeric, dimeric, and a previously undescribed tetrameric form of pig heart lipoamide dehydrogenase (LADH), a mitochondrial matrix enzyme. Dynamic light scattering studies of native LADH in aqueous solution indicate that lowering pH favors a shift in average molecular mass from higher oligomeric states to monomer. Sedimentation velocity of LADH entrapped in reverse micelles reveals dimer and tetramer at both pH 5.8 and 7.5, but monomer was observed only at pH 5.8. Enzyme activity measurements in reverse Aerosol OT micelles in octane indicate that LADH dimer and tetramer possess lipoamide dehydrogenase and diaphorase activities at pH 7.5. Upon acidification to pH 5.8 only the LADH monomer is active and only the diaphorase activity is observed. These results indicate a correlation between pH-dependent changes in the LADH reaction specificity and its oligomeric state. The acidification of mitochondrial matrix that occurs during ischemia-reperfusion injury is sufficient to alter the structure and enzymatic specificity of LADH, thereby reducing mitochondrial defenses, increasing oxidative stress, and slowing the recovery of energy metabolism. Matrix acidification may also disrupt the quaternary structure of other mitochondrial protein complexes critical for cellular homeostasis and survival. collapse abstract
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FEBS letters 2003 Nov; 554(3)
Relationship between intramolecular hydrogen bonding and solvent accessibility of side-chain donors and acceptors in proteins.
This study shows that intramolecular hydrogen bonding in proteins depends on the accessibility of donors and acceptors to water molecules. The frequency of occurrence of H-bonded side chains in proteins is inversely proportional to the solvent access... expand abstractibility of their donors and acceptors. Estimates of the notional free energy of hydrogen bonding suggest that intramolecular hydrogen-bonding interactions of buried and half-buried donors and acceptors can contribute favorably to the stability of a protein, whereas those of solvent-exposed polar atoms become less favorable or unfavorable. collapse abstract
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Molekuliarnaia biologiia 37(3)
A comparative analysis of interhelical polar interactions of various alpha-helix packings in proteins
One hundred twenty globular proteins and forty five "leucine zippers" representing all types of packing of long alpha-helices were studied in terms of revealing and comparing their interhelical hydrogen and salt bonds. Many previous studies of "leuci... expand abstractne zippers" and their analogs showed that interhelical interactions between polar groups could impart specificity to packing of an alpha-helix. The current comparison demonstrated that basically, globular proteins and "leucine zippers" had similar interhelical polar interactions with presumably a similar structural role. However, depending on packing of alpha-helices, the networks of interhelical polar bonds were shown to be distinct and determined both by physicochemical properties of involved amino acid residues and by the relative positions of hydrophobic and hydrophilic residues on the surface of alpha-helices. The revealed distinction is probably crucial for selecting the unique packing of an alpha-helix. collapse abstract
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Molekuliarnaia biologiia 36(1)
Systematic analysis of buried polar side chains and their interactions in alpha-helical proteins
Examination of 80 alpha-helical proteins and domains demonstrates that they contain from 1 to more than 20 completely buried (water-inaccessible) polar side chains. As a rule the latter have partners for H-bonding but the resulting H-bond system is o... expand abstractften not exhaustive. Basing on statistical analysis, we determined the optimal number of H-bonds for every type of polar side chain, and discuss the structural role of vacant donors and acceptors. About half of the H-bonds formed by buried side chains pertain to interhelix contacts of the (side chain)-(side chain) and (side chain)-(main chain) types. Such interactions appear to be a most important factor determining the mutual arrangement of alpha-helices in proteins. Analysis of the frequency of occurrence of various interacting pairs reveals that these interactions are selective. collapse abstract
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Molekuliarnaia biologiia 35(1)
Structure of alpha-spiral hairpins with short connections in globular proteins
The analysis of conformations of more than 100 alpha-alpha-hairpins with closely packed helical segments and connections up to four amino acid residues in length was carried out. Five types of the connections were revealed and their phi and psi value... expand abstracts on the Ramachandran map were found. Each type of alpha-alpha-hairpins was shown to have a unique sequence pattern for hydrophobic and hydrophilic residues. collapse abstract
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FEBS letters 1999 Dec; 463(1-2)
Complementary packing of alpha-helices in proteins.
The packing of alpha-helices in proteins is restricted by both the principle of close packing and the chemical nature of side chains. As a result, (1) alpha-helical surfaces forming the interface should be complementary to each other, (2) hydrophobic... expand abstract stripes of the alpha-helices should fit together like pieces of a jigsaw puzzle, and (3) buried polar side chains (if there are any) should be arranged in a complementary fashion. collapse abstract
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FEBS letters 1998 Oct; 437(3)
A structural tree for proteins containing S-like beta-sheets.
A structural tree for proteins and domains containing S-like beta-sheets has been constructed. An S-like beta-sheet is taken as a starting structure in modelling or as a root structure of the tree. Larger structures are obtained by a stepwise additio... expand abstractn of beta-strands and/or alpha-helices to the root S-like beta-sheet in accordance with a restricted set of rules inferred from known principles of protein structure. Applications of the structural tree to structure comparison, protein classification and protein folding are described. collapse abstract
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Bioorganicheskaia khimiia 1998 Jun; 24(7)
Architecture of compact three alpha-helical structures
Modeling and methodical analysis of possible compact spatial arrangements of three alpha helices bound with connections were carried out. It was suggested to describe the compact three-alpha-helical structures as combinations of alpha-helical hairpin... expand abstracts, L-shaped structures, V-shaped structures, alpha-alpha comers, and alpha-l-alpha motifs. Practically all the structures resulting from such a modeling were shown to exist in globular proteins. Many small proteins and domains were found to consist of only these three-helical structures. This indicated that each such three-helical structure was stable by itself and capable of independent folding of its polypeptide chain into this structure. collapse abstract
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Proteins 1997 May; 28(2)
Structural trees for protein superfamilies.
Structural trees for large protein superfamilies, such as beta proteins with the aligned beta sheet packing, beta proteins with the orthogonal packing of alpha helices, two-layer and three-layer alpha/beta proteins, have been constructed. The structu... expand abstractral motifs having unique overall folds and a unique handedness are taken as root structures of the trees. The larger protein structures of each superfamily are obtained by a stepwise addition of alpha helices and/or beta strands to the corresponding root motif, taking into account a restricted set of rules inferred from known principles of the protein structure. Among these rules, prohibition of crossing connections, attention to handedness and compactness, and a requirement for alpha helices to be packed in alpha-helical layers and beta strands in beta layers are the most important. Proteins and domains whose structures can be obtained by stepwise addition of alpha helices and/or beta strands to the same root motif can be grouped into one structural class or a superfamily. Proteins and domains found within branches of a structural tree can be grouped into subclasses or subfamilies. Levels of structural similarity between different proteins can easily be observed by visual inspection. Within one branch, protein structures having a higher position in the tree include the structures located lower. Proteins and domains of different branches have the structure located in the branching point as the common fold. collapse abstract
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FEBS letters 1997 Apr; 407(1)
A structural tree for proteins containing 3beta-corners.
A structural tree for beta-proteins with predominantly orthogonal beta-sheet packing has been constructed. The 3beta-corner, a structural motif that recurs in proteins of this class, is taken as a root structure of the tree. The 3beta-corner can be r... expand abstractepresented as a triple-stranded beta-sheet folded on to itself so that its two beta-beta-hairpins are packed approximately orthogonally in different layers and the central strand bends by approximately 90 degrees in a right-handed direction when passing from one layer to the other. The larger protein structures are obtained by stepwise addition of beta-strands to the root 3beta-corner taking into account a restricted set of rules inferred from known principles of protein structure. The protein structures that can be obtained in this way are grouped into one structural class and those found in branches of the structural tree into subclasses. collapse abstract
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Bioorganicheskaia khimiia 1997 Mar; 23(4)
New structural motifs in alpha-helical proteins
Four novel structural motifs were found and characterized in alpha-helical proteins. One of them consists of three alpha helices and can be represented as a combination of an alpha-alpha corner and an L-shaped structure. Its second alpha helix is a p... expand abstractart of both one of the two alpha helices of the alpha-alpha corner and one of the two L-structure helices. The second structural motif, named the ABCD unit, consists of four alpha helices A, B, C, and D. These are consecutive in sequence and arranged in space in such a manner that the helices B, C, and D form a left-handed superhelix and the helix A is located between the helices B and D and is approximately antiparallel to them. The third motif, alpha helix-loop-alpha helix, consists of two alpha helices and a long connection. Its alpha helices are arranged in an approximately parallel manner and together with the long connection, form a left-handed alpha-1-alpha superhelix in space. The fourth structural motif considered is formed by four consecutive alpha helices. It is named the phi motif, because its overall shape is reminiscent of the Greek letter phi. Various variants of these motifs are analyzed on numerous examples of proteins with the known spatial structures. collapse abstract
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FEBS letters 1996 Aug; 391(1-2)
A structural tree for alpha-helical proteins containing alpha-alpha-corners and its application to protein classification.
A structural tree for alpha-helical proteins and domains including alpha-alpha-corners has been constructed. The alpha-alpha-corner is taken as a root structure of the tree. The larger protein structures are obtained by stepwise addition of alpha-hel... expand abstractices to the root alpha-alpha-corner taking into account a restricted set of rules inferred from known principles of protein structure. The protein structures that can be obtained in this way are grouped into one structural class and those found in branches of the tree into subclasses. collapse abstract
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