A folding space odyssey

Davidson, Alan R.

doi:10.1073/pnas.0800030105

Cited by 23 publications

(18 citation statements)

References 18 publications

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“…As examples of protein fold evolution are very difficult to identify and prove (25), further studies using the same approaches as we have used could lead to important progress in this field. We are confident that mechanisms similar to those described here may account for the evolution of many other large multiprotein complexes.…”

Section: Discussionmentioning

confidence: 99%

Phages have adapted the same protein fold to fulfill multiple functions in virion assembly

Cardarelli¹,

Pell

Neudecker

et al. 2010

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

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Evolutionary relationships may exist among very diverse groups of proteins even though they perform different functions and display little sequence similarity. The tailed bacteriophages present a uniquely amenable system for identifying such groups because of their huge diversity yet conserved genome structures. In this work, we used structural, functional, and genomic context comparisons to conclude that the head–tail connector protein and tail tube protein of bacteriophage λ diverged from a common ancestral protein. Further comparisons of tertiary and quaternary structures indicate that the baseplate hub and tail terminator proteins of bacteriophage may also be part of this same family. We propose that all of these proteins evolved from a single ancestral tail tube protein fold, and that gene duplication followed by differentiation led to the specialized roles of these proteins seen in bacteriophages today. Although this type of evolutionary mechanism has been proposed for other systems, our work provides an evolutionary mechanism for a group of proteins with different functions that bear no sequence similarity. Our data also indicate that the addition of a structural element at the N terminus of the λ head–tail connector protein endows it with a distinctive protein interaction capability compared with many of its putative homologues.

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Section: Discussionmentioning

confidence: 99%

Phages have adapted the same protein fold to fulfill multiple functions in virion assembly

Cardarelli¹,

Pell

Neudecker

et al. 2010

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

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“…9 Nevertheless, different folds for proteins with high-sequence identity (>30%) also have been identified in recent years, and such cases may provide insight into the evolution of the wide array of protein folds found in nature. 10 In an effort to enhance our understanding of this evolution of protein folds and fold switching, multiple pairs of proteins with sequence identities of up to 95% but distinctly different folds have been designed and studied experimentally by NMR spectroscopy. [11][12][13] As expected, comparative modeling approaches have difficulties in selecting the correct template from the known threedimensional structures when their sequences but not their structures converge, making it challenging to build the correct tertiary structure by this approach.…”

Section: Introductionmentioning

confidence: 99%

De novo structure generation using chemical shifts for proteins with high‐sequence identity but different folds

Shen

Bryan

et al. 2010

Protein Science

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Proteins with high-sequence identity but very different folds present a special challenge to sequence-based protein structure prediction methods. In particular, a 56-residue three-helical bundle protein (GA 95 ) and an a/b-fold protein (GB 95 ), which share 95% sequence identity, were targets in the CASP-8 structure prediction contest. With only 12 out of 300 submitted server-CASP8 models for GA 95

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“…A relevant example is provided by the family of phage Cro transcription factors; one member, P22 Cro, is an all-␣ protein whereas another member, Cro, is a mixed ␣/␤ protein. Although described as belonging to different folds (19-21), there are local structural similarities between these proteins that reveal important functional information: Both proteins contain helix-turnhelix DNA binding motifs that superimpose to 1.6 Å rmsd.Although the existence of structural fragments with a common function is implicit in recent discussions of the evolution of protein folds (16,18,21), they have not, to our knowledge, been used as part of a general strategy for function annotation. Here, we suggest how this goal can be realized.…”

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confidence: 99%

Structural relationships among proteins with different global topologies and their implications for function annotation strategies

Petrey

Fischer

Honig

2009

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

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It has become increasingly apparent that geometric relationships often exist between regions of two proteins that have quite different global topologies or folds. In this article, we examine whether such relationships can be used to infer a functional connection between the two proteins in question. We find, by considering a number of examples involving metal and cation binding, sugar binding, and aromatic group binding, that geometrically similar protein fragments can share related functions, even if they have been classified as belonging to different folds and topologies. Thus, the use of classifications inevitably limits the number of functional inferences that can be obtained from the comparative analysis of protein structures. In contrast, the development of interactive computational tools that recognize the ''continuous'' nature of protein structure/function space, by increasing the number of potentially meaningful relationships that are considered, may offer a dramatic enhancement in the ability to extract information from protein structure databases. We introduce the MarkUs server, that embodies this strategy and that is designed for a user interested in developing and validating specific functional hypotheses.protein fold space ͉ protein function annotation ͉ protein structure alignment ͉ protein structure similarity T he identification of structural and functional relationships between proteins based on similarities in their amino acid sequence is an essential component of modern biology. It has been recognized for some time that two proteins can be similar to one another in structure despite a lack of any detectable sequence similarity and that this information can be used to assign function. There has been considerable discussion over the past several years as to how structural similarities can most usefully be described (1-8). Widely used databases such as SCOP (9) and CATH (10) describe relationships between proteins using a hierarchy of classifications that reflect similarities in the spatial organization of secondary structure elements (SSEs). For example, proteins with the same overall SSE composition are described as belonging to the same ''class,'' and proteins with similar spatial arrangements of SSE's are described as belonging to the same ''fold'' or ''topology.'' Classification implies discreteness in the organization of structure space in that a protein that is assigned to one class or fold will not belong to another.An alternative view suggests that protein structure space should be viewed as ''continuous'' rather than discrete (1,2,6,8). Indeed, it has become apparent that structural relationships between protein domains exist at various scales; from small sets of SSE's (4), to larger fragments (1, 2), even when the proteins have been assigned to different folds and structural classes (3). Such structural and/or functional relationships between fragments of two different proteins have been extensively discussed (5, 7, 11, 12) and pose serious challenges to hierarchical classification sc...

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A folding space odyssey

Cited by 23 publications

References 18 publications

Phages have adapted the same protein fold to fulfill multiple functions in virion assembly

Phages have adapted the same protein fold to fulfill multiple functions in virion assembly

De novo structure generation using chemical shifts for proteins with high‐sequence identity but different folds

Structural relationships among proteins with different global topologies and their implications for function annotation strategies

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