Distant homology recognition using structural classification of proteins

Murzin, Alexey G.; Bateman, Alex

doi:10.1002/(sici)1097-0134(1997)1+<105::aid-prot14>3.3.co;2-1

Cited by 39 publications

(24 citation statements)

References 31 publications

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“…Evolution would be mainly divergent with all proteins arising from a limited number of ancestors. Each ancestor would give rise to a superfamily with members that have diverged beyond presently accessible significant sequence similarity but have kept a similar fold and some characteristics related to their function 33. These superfamilies often possess a very stable fold 34.…”

Section: Discussionmentioning

confidence: 99%

Sequence and structural features of the T-fold, an original tunnelling building unit

2000

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A similar fold has been found in four archetype enzymes that perform different functions. This new fold has been named the T-fold because it is found in multimeric proteins crossed by a tunnel. The T-fold consists of an antiparallel beta-sheet of four sequential strands, and two antiparallel helices between the second and third strand, layered on the concave side of the beta-sheet. The presently known T-fold proteins share a high structural similarity (a mean of 1.4 A root mean square (r.m.s.) deviation on the common core) while they only exhibit a low level of sequence identity (a mean of 10.5% on the aligned regions). They bind to substrates belonging to the purine or pterin families, and share a fold-related binding site with a glutamate or glutamine residue anchoring the substrate and a lot of conserved interactions. They also share a similar oligomerization mode: several T-folds join together to form a beta(2n)alpha(n) barrel, then two barrels join together in a head-to-head fashion to made up the native enzymes. The T-fold has the characteristics of a globular domain, with a hydrophobic core and a clearly defined topohydrophobic network. It defines a new class of common folds or recurrent domains found in distantly related proteins. However, it is likely not stable in monomeric form and until now is only observed in association with other T-folds through multimerization. Proteins 2000;39:142-154.

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Section: Discussionmentioning

confidence: 99%

Sequence and structural features of the T-fold, an original tunnelling building unit

2000

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“…23,45,51 Such instances of different folds-with similar architectures and clear evidence of homology, yet distinct topologies-can serve as helpful starting points in developing approaches to identify cases of similar architecture which do not show clear sequence or topological relationships (essentially, they could serve as true positives). 23,45,51 Such instances of different folds-with similar architectures and clear evidence of homology, yet distinct topologies-can serve as helpful starting points in developing approaches to identify cases of similar architecture which do not show clear sequence or topological relationships (essentially, they could serve as true positives).…”

Section: Conclusion Outlookmentioning

confidence: 99%

The Urfold: Structural similarity just above the superfold level?

2019

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We suspect that there is a level of granularity of protein structure intermediate between the classical levels of "architecture" and "topology," as reflected in such phenomena as extensive three-dimensional structural similarity above the level of (super)folds. Here, we examine this notion of architectural identity despite topological variability, starting with a concept that we call the "Urfold." We believe that this model could offer a new conceptual approach for protein structural analysis and classification:indeed, the Urfold concept may help reconcile various phenomena that have been frequently recognized or debated for years, such as the precise meaning of "significant" structural overlap and the degree of continuity of fold space. More broadly, the role of structural similarity in sequence$structure$function evolution has been studied via many models over the years; by addressing a conceptual gap that we believe exists between the architecture and topology levels of structural classification schemes, the Urfold eventually may help synthesize these models into a generalized, consistent framework. Here, we begin by qualitatively introducing the concept. K E Y W O R D Sarchitecture, fold space, molecular evolution, protein structure classification, secondary structure, superfold, topology, β-sheet Abbreviations: FS, fold space; PSS, protein structure space; SBB, small β-barrel; SSE, secondary structural element.

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“…Proteins with unalignable amino acid sequences can have very similar 3D structures (Murzin and Bateman 1997). Single-stranded RNAs with dissimilar sequences can fold into identical secondary structures (Schuster et al 1994) (e.g., AAAAAGGGTTTTT and GGGGGTTTCCCCC).…”

Section: Introductionmentioning

confidence: 99%

Genome-Level Analysis of Selective Constraint without Apparent Sequence Conservation

Vakhrusheva

Bazykin

Kondrashov

2013

Genome Biology and Evolution

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Conservation of function can be accompanied by obvious similarity of homologous sequences which may persist for billions of years (Iyer LM, Leipe DD, Koonin EV, Aravind L. 2004. Evolutionary history and higher order classification of AAA+ ATPases. J Struct Biol. 146:11–31.). However, presumably homologous segments of noncoding DNA can also retain their ancestral function even after their sequences diverge beyond recognition (Fisher S, Grice EA, Vinton RM, Bessling SL, McCallion AS. 2006. Conservation of RET regulatory function from human to zebrafish without sequence similarity. Science 312:276–279.). To investigate this phenomenon at the genomic scale, we studied homologous introns in a quartet of insect species, and in a quartet of vertebrate species. Each quartet consisted of two pairs of moderately distant genomes, with a much larger evolutionary distance between the pairs. In both quartets, we found that introns that carry a regulatory segment or a conserved segment in the first pair tend to carry a conserved segment in the second pair, even though no similarity of these segments could be detected between the two pairs. Furthermore, introns from one pair that are preserved in the other pair tend to carry a conserved segment within the first pair, and be longer in the first pair, compared with the introns that were lost between pairs, even though no similarity between pairs could be detected in such preserved introns. These results indicate that selective constraint, presumably caused by conservation of the ancestral function, often persists even after the homologous DNA segments become unalignable.

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Distant homology recognition using structural classification of proteins

Cited by 39 publications

References 31 publications

Sequence and structural features of the T-fold, an original tunnelling building unit

Sequence and structural features of the T-fold, an original tunnelling building unit

The Urfold: Structural similarity just above the superfold level?

Genome-Level Analysis of Selective Constraint without Apparent Sequence Conservation

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