Use of pair potentials across protein interfaces in screening predicted docked complexes

Moont, Gidon; Gabb, Henry A.; Sternberg, Michael J. E.

doi:10.1002/(sici)1097-0134(19990515)35:3<364::aid-prot11>3.0.co;2-4

Cited by 244 publications

(151 citation statements)

References 58 publications

(2 reference statements)

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“…The residue-pairing score came from associating the residue pairs in the interfacial area with likelihood statistics observed for those pairs in high resolution X-Ray structures. 55 The residue-pairing score compliments well the RDC correlation score as there are multiple minima in the RDC score due to the shape degeneracy of the dimer models The pairing scores ranged from 10.96 for the most favorable pairs to À10.41 for the least favorable. The best dimeric models were selected based on a set of criteria including a Pearson correlation coefficient for RDC comparisons >0.80 and a sum of residue-pairing scores >0.…”

Section: Grid Search Algorithm and Model Evaluationsmentioning

confidence: 99%

Three‐dimensional structure of the weakly associated protein homodimer SeR13 using RDCs and paramagnetic surface mapping

et al. 2010

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The traditional NMR-based method for determining oligomeric protein structure usually involves distinguishing and assigning intra-and intersubunit NOEs. This task becomes challenging when determining symmetric homo-dimer structures because NOE cross-peaks from a given pair of protons occur at the same position whether intra-or intersubunit in origin. While there are isotope-filtering strategies for distinguishing intra from intermolecular NOE interactions in these cases, they are laborious and often prove ineffectual in cases of weak dimers, where observation of intermolecular NOEs is rare. Here, we present an efficient procedure for weak dimer structure determination based on residual dipolar couplings (RDCs), chemical shift changes upon dilution, and paramagnetic surface perturbations. This procedure is applied to the Northeast Structural Genomics Consortium protein target, SeR13, a negatively charged Staphylococcus epidermidis dimeric protein (K d 3.4 6 1.4 mM) composed of 86 amino acids. A structure determination for the monomeric form using traditional NMR methods is presented, followed by a dimer structure determination using docking under orientation constraints from RDCs data, and scoring under residue pair potentials and shape-based predictions of RDCs. Validation using paramagnetic surface perturbation and chemical shift perturbation data acquired on sample dilution is also presented. The general utility of the dimer structure determination procedure and the possible relevance of SeR13 dimer formation are discussed.

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Section: Grid Search Algorithm and Model Evaluationsmentioning

confidence: 99%

Three‐dimensional structure of the weakly associated protein homodimer SeR13 using RDCs and paramagnetic surface mapping

et al. 2010

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“…Among them, the widely used residue level pair potential score (RPScore) was derived from a statistical analysis of pairwise interactions at complex interfaces and was reported to efficiently select near-native structures from a set of decoys (38). All of the docking solutions generated from the intramolecular and intermolecular databases were scored with the RPScore.…”

Section: Optimization Of Scotch By Using a Statistical Pairwise Potenmentioning

confidence: 99%

Coevolution at protein complex interfaces can be detected by the complementarity trace with important impact for predictive docking

Madaoui

Guérois

2008

Proc. Natl. Acad. Sci. U.S.A.

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Protein surfaces are under significant selection pressure to maintain interactions with their partners throughout evolution. Capturing how selection pressure acts at the interfaces of proteinprotein complexes is a fundamental issue with high interest for the structural prediction of macromolecular assemblies. We tackled this issue under the assumption that, throughout evolution, mutations should minimally disrupt the physicochemical compatibility between specific clusters of interacting residues. This constraint drove the development of the so-called Surface COmplementarity Trace in Complex History score (SCOTCH), which was found to discriminate with high efficiency the structure of biological complexes. SCOTCH performances were assessed not only with respect to other evolution-based approaches, such as conservation and coevolution analyses, but also with respect to statistically based scoring methods. Validated on a set of 129 complexes of known structure exhibiting both permanent and transient intermolecular interactions, SCOTCH appears as a robust strategy to guide the prediction of protein-protein complex structures. Of particular interest, it also provides a basic framework to efficiently track how protein surfaces could evolve while keeping their partners in contact.evolution ͉ prediction ͉ protein-protein interaction T he modular assembly of proteins is a key determinant in the regulation of biological systems. Combinations of inter-and intramolecular interactions hold the cell machineries and govern the flow of information transmitted through cell signaling pathways. To unravel the complexity of cell organization, atlases of the physical interactome have been obtained for several model organisms (1, 2). To further elucidate the competitions and synergies ruling the molecular logic of these protein-protein interaction networks, a critical step relies on the structural characterization of the protein complexes. However, there is still a huge gap between the proteome-wide data accumulating and the available structural details of macromolecular complexes.A number of studies have tackled the large-scale analysis of protein-protein complexes from a structural perspective (3-7). They have emphasized that size, shape, and the physicochemical complementarities at the interfaces are key descriptors that could be used to develop computational methods able to predict protein-binding sites from sequences or structures (8)(9)(10)(11)(12)(13)(14). In the context of evolution, seminal studies compared the binding modes of domain-domain interactions between homologous proteins and concluded that they tend to interact similarly, even if sequence identity has been maintained as low as 30% (15, 16). Such a low conservation threshold suggests that interaction surfaces can evolve significantly while maintaining sufficient specificity between the binding partners. The paradox between sequence divergence and structural conservation of macromolecular assemblies has been recently related to the notion of superfamily, and the exis...

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“…The Bcl-3 ARD structure and the (p50) 2 homodimer were superimposed onto the I B␣⅐NF-B complex. Pirin was then docked to the Bcl-3⅐(p50) 2 complex using the program FTDOCK (40). The surface of Pirin has a large acidic patch on the N-terminal domain surface formed by residues 77-82, 97-103, and 124 -128.…”

Section: Resultsmentioning

confidence: 99%

Crystal Structure of Human Pirin

Pang

Bartlam

Zeng

et al. 2004

Journal of Biological Chemistry

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Pirin is a newly identified nuclear protein that interacts with the oncoprotein B-cell lymphoma 3-encoded (Bcl-3) and nuclear factor I (NFI). The crystal structure of human Pirin at 2.1-Å resolution shows it to be a member of the functionally diverse cupin superfamily. The structure comprises two ␤-barrel domains, with an Fe(II) cofactor bound within the cavity of the N-terminal domain. These findings suggest an enzymatic role for Pirin, most likely in biological redox reactions involving oxygen, and provide compelling evidence that Pirin requires the participation of the metal ion for its interaction with Bcl-3 to co-regulate the NF-B transcription pathway and the interaction with NFI in DNA replication. Substitution of iron by heavy metals thus provides a novel pathway for these metals to directly influence gene transcription. The structure suggests an interesting new role of iron in biology and that Pirin may be involved in novel mechanisms of gene regulation.Pirin is a newly identified nuclear protein that is widely expressed in dot-like subnuclear structures in human tissues, in particular liver and heart (1). Pirins are highly conserved among mammals, plants, fungi, and even prokaryotic organisms and have been assigned as a sub-family of the cupin superfamily based on both structure and sequence homology (1, 2). The cupin superfamily is among the most functionally diverse of any protein family described to date, with both enzymatic and non-enzymatic members included (2). This cupin superfamily is grouped according to a conserved ␤-barrel fold and two characteristic sequence motifs. Study of Pirin reveals two cupin domains from its primary sequence that are consistent with other members of the superfamily.The exact functions of Pirins are not yet known. No enzymatic activity has been described, but human Pirin has been found to bind to the nuclear factor I/CCAAT box transcription factor (NFI) 1 and to the oncoprotein B cell lymphoma 3-encoded (Bcl-3) in vivo (1, 3), suggesting that it is a transcription cofactor. NFI is known to stimulate DNA replication and RNA polymerase II-driven transcription (4). Bcl-3 is a distinctive member of the I B family, which inhibits the transcription factor NF-B by preventing NF-B nuclear translocation and DNA binding. However, there is also evidence that Bcl-3 preferentially binds to NF-B p50 or p52 homodimers to stimulate transcription (5). The functional nature of this difference between I B (inhibiting) and Bcl-3 (enhancing) is not known, but it is clear that they bind to different protein partners. Pirin is one of four binding partners of Bcl-3, together with Bard1, Tip60, and Jab1, and can be sequestered into quaternary complexes with Bcl-3, p50, and DNA (3). These four Bcl-3-interacting protein partners, which do not share any sequence homology, might play some crucial role in regulating the function of Bcl-3 and I B. Indeed, both Pirin and Bcl-3 are localized in the nucleus, and the potential roles of Pirin in NF-B-dependent transcriptional regulation are implicated i...

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Use of pair potentials across protein interfaces in screening predicted docked complexes

Cited by 244 publications

References 58 publications

Three‐dimensional structure of the weakly associated protein homodimer SeR13 using RDCs and paramagnetic surface mapping

Three‐dimensional structure of the weakly associated protein homodimer SeR13 using RDCs and paramagnetic surface mapping

Coevolution at protein complex interfaces can be detected by the complementarity trace with important impact for predictive docking

Crystal Structure of Human Pirin

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