Similarities of protein topologies: evolutionary divergence, functional convergence or principles of folding?

Ptitsyn, Oleg B.; Finkelstein, Alan

doi:10.1017/s0033583500001724

Cited by 195 publications

(117 citation statements)

References 95 publications

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“…This inference is further confirmed by the presence of non-random coil peaks in the NMR spectrum at 4 M urea. According to the molecular theory of protein structure (proposed by (49,50) and supported by (51-53)), the secondary structure of the unfolded state fluctuates around its nativelike structure, and similarly, the residual secondary and tertiary structures are native-like in the partly condensed state (49)(50)(51)(52)(53). In the partly condensed (I2) state of CPR3, some regions (a1 and nearby regions) appear to exist in the native-like position in 3D space, which can be observed in the 15 N-HSQC spectrum having some non-random coil peaks with chemical shift similar to that in the native state.…”

Section: Discussionmentioning

confidence: 99%

Unfolding of CPR3 Gets Initiated at the Active Site and Proceeds via Two Intermediates

Shukla

Singh

Vispute

et al. 2017

Biophysical Journal

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Cyclophilin catalyzes the ubiquitous process ''peptidyl-prolyl cis-trans isomerization,'' which plays a key role in protein folding, regulation, and function. Here, we present a detailed characterization of the unfolding of yeast mitochondrial cyclophilin (CPR3) induced by urea. It is seen that CPR3 unfolding is reversible and proceeds via two intermediates, I1 and I2. The I1 state has native-like secondary structure and shows strong anilino-8-naphthalenesulphonate binding due to increased exposure of the solvent-accessible cluster of non-polar groups. Thus, it has some features of a molten globule. The I2 state is more unfolded, but it retains some residual secondary structure, and shows weak anilino-8-naphthalenesulphonate binding. Chemical shift perturbation analysis by 1 H-15 N heteronuclear single quantum coherence spectra reveals disruption of the tertiary contacts among the regions close to the active site in the first step of unfolding, i.e., the N-I1 transition. Both of the intermediates, I1 and I2, showed a propensity to self-associate under stirring conditions, but their kinetic profiles are different; the native protein did not show any such tendency under the same conditions. All these observations could have significant implications for the function of the protein.

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Section: Discussionmentioning

confidence: 99%

Unfolding of CPR3 Gets Initiated at the Active Site and Proceeds via Two Intermediates

Shukla

Singh

Vispute

et al. 2017

Biophysical Journal

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“…One of the most striking discoveries in structural biology is highly uneven distribution of protein fold usage (1)(2)(3)(4)(5)The ability of protein structures to accommodate many unrelated sequences was demonstrated in theory and simulations and is generally understood on theoretical grounds (6)(7)(8)(9). At the same time, the observation that only certain protein structures form superfamilies while others do not and that the size of superfamilies varies greatly, represents one of the major puzzles in structural biology.…”

Section: Introductionmentioning

confidence: 99%

Physical Origins of Protein Superfamilies

Zeldovich

Berezovsky

Shakhnovich

2006

Journal of Molecular Biology

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In this work, we discovered a fundamental connection between selection for protein stability and emergence of preferred structures of proteins. Using standard exact 3-dimensional lattice model we evolve sequences starting from random ones and determining exact native structure after each mutation. Acceptance of mutations is biased to select for stable proteins. We found that certain structures, "wonderfolds", are independently discovered numerous times as native states of stable proteins in many unrelated runs of selection. Diversity of sequences that fold into wonderfold structures gives rise to superfamilies, i.e. sets of dissimilar sequences that fold into the same or very similar structures. Wonderfolds appear to be the most designable structures out of complete set of compact lattice proteins. Furthermore, proteins having wondefolds as their native structure tend to be most thermostable among all evolved proteins. This effect is purely due to the favorable geometric properties of wonderfolds and, thus, dominates any dependence on sequences. The present work establishes a model of prebiotic structure selection, which identifies dominant structural patterns emerging upon optimization of proteins for survival in hot environment. Convergently discovered prebiotic initial superfamilies with ''wonderfold'' structures could have served as a seed for subsequent biological evolution involving gene duplications and divergence.3

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“…We introduce the concept of a network of kinship relations, which is intended to locate essentially all ␤-sheet-containing protein domains. We focus our attention on ␤-sheet topology (Richardson 1977;Ptitsyn and Finkelstein 1980), that is, the directions of individual ␤-strands and their connectivity (Fig. 1A).…”

Section: Construction Of a Global Fold Kinship Relations Networkmentioning

confidence: 99%

Finding evolutionary relations beyond superfamilies : Fold-based superfamilies

Matsuda¹,

Kawabata²,

Kinoshita³

et al. 2003

Biophysics

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Superfamily classifications are based variably on similarity of sequences, global folds, local structures, or functions. We have examined the possibility of defining superfamilies purely from the viewpoint of the global fold/function relationship. For this purpose, we first classified protein domains according to the ␤-sheet topology. We then introduced the concept of kinship relations among the classified ␤-sheet topology by assuming that the major elementary event leading to creation of a new ␤-sheet topology is either an addition or deletion of one ␤-strand at the edge of an existing ␤-sheet during the molecular evolution. Based on this kinship relation, a network of protein domains was constructed so that the distance between a pair of domains represents the number of evolutionary events that lead one from the other domain. We then mapped on it all known domains with a specific core chemical function (here taken, as an example, that involving ATP or its analogs). Careful analyses revealed that the domains are found distributed on the network as >20 mutually disjointed clusters. The proteins in each cluster are defined to form a fold-based superfamily. The results indicate that >20 ATP-binding protein superfamilies have been invented independently in the process of molecular evolution, and the conservative evolutionary diffusion of global folds and functions is the origin of the relationship between them.

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Similarities of protein topologies: evolutionary divergence, functional convergence or principles of folding?

Cited by 195 publications

References 95 publications

Unfolding of CPR3 Gets Initiated at the Active Site and Proceeds via Two Intermediates

Unfolding of CPR3 Gets Initiated at the Active Site and Proceeds via Two Intermediates

Physical Origins of Protein Superfamilies

Finding evolutionary relations beyond superfamilies : Fold-based superfamilies

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