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The GD box: a widespread noncontiguous supersecondary structural element.

ABSTRACT: Identification and characterization of recurrent supersecondary structural elements is central to understanding the rules governing protein tertiary structure. Here, we describe the GD box, a widespread noncontiguous supersecondary element, which we initially found in a group of topologically distinct but homologous beta-barrels--the cradle-loop barrels. The GD box is similar both in sequence and structure and comprises two short unpaired beta-strands connected by an orthogonal type-II beta-turn and a noncontiguous beta-strand forming hydrogen bonds with the beta-turn. Using structure-based analysis, we have detected 518 instances of the GD box in a nonredundant subset of the SCOP database comprising 3771 domains. Apart from the cradle-loop barrels, this motif is also found in a diverse set of nonhomologous folds including other topologically related beta-barrels. Since nonlocal interactions are fundamental in the formation of protein structure, systematic identification and characterization of other noncontiguous supersecondary structural elements is likely to prove valuable to protein structure modeling, validation, and prediction.

SUBMITTER: Alva V

PROVIDER: S-EPMC2777370 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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The GD box: a widespread noncontiguous supersecondary structural element.

Alva Vikram V Dunin-Horkawicz Stanislaw S Habeck Michael M Coles Murray M Lupas Andrei N AN

Protein science : a publication of the Protein Society 20090901 9

Identification and characterization of recurrent supersecondary structural elements is central to understanding the rules governing protein tertiary structure. Here, we describe the GD box, a widespread noncontiguous supersecondary element, which we initially found in a group of topologically distinct but homologous beta-barrels--the cradle-loop barrels. The GD box is similar both in sequence and structure and comprises two short unpaired beta-strands connected by an orthogonal type-II beta-turn ...[more]

PMID: 19609930

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Project description:BackgroundThe Asp-box is a short sequence and structure motif that folds as a well-defined beta-hairpin. It is present in different folds, but occurs most prominently as repeats in beta-propellers. Asp-box beta-propellers are known to be characteristically irregular and to occur in many medically important proteins, most of which are glycosidase enzymes, but they are otherwise not well characterized and are only rarely treated as a distinct beta-propeller family. We have analyzed the sequence, structure, function and occurrence of the Asp-box and s-Asp-box -a related shorter variant, and provide a comprehensive classification and computational analysis of the Asp-box beta-propeller family.ResultsWe find that all conserved residues of the Asp-box support its structure, whereas the residues in variable positions are generally used for other purposes. The Asp-box clearly has a structural role in beta-propellers and is highly unlikely to be involved in ligand binding. Sequence analysis of the Asp-box beta-propeller family reveals it to be very widespread especially in bacteria and suggests a wide functional range. Disregarding the Asp-boxes, sequence conservation of the propeller blades is very low, but a distinct pattern of residues with specific properties have been identified. Interestingly, Asp-boxes are occasionally found very close to other propeller-associated repeats in extensive mixed-motif stretches, which strongly suggests the existence of a novel class of hybrid beta-propellers. Structural analysis reveals that the top and bottom faces of Asp-box beta-propellers have striking and consistently different loop properties; the bottom is structurally conserved whereas the top shows great structural variation. Interestingly, only the top face is used for functional purposes in known structures. A structural analysis of the 10-bladed beta-propeller fold, which has so far only been observed in the Asp-box family, reveals that the inner strands of the blades are unusually far apart, which explains the surprisingly large diameter of the central tunnel of sortilin.ConclusionWe have provided new insight into the structure and function of the Asp-box motif and of Asp-box beta-propellers, and expect that the classification and analysis presented here will prove helpful in interpreting future data on Asp-box proteins in general and on Asp-box beta-propellers in particular.

Project description:We will consider in this chapter supersecondary structures (SSS) as a set of secondary structure elements (SSEs) found in protein domains. Some SSS arrangements/topologies have been consistently observed within known tertiary structural domains. We use them in the context of repeating supersecondary structures that self-assemble in a symmetric arrangement to form a domain. We call them protodomains (or protofolds). Protodomains are some of the most interesting and insightful SSSs. Within a given 3D protein domain/fold, recognizing such sets may give insights into a possible evolutionary process of duplication, fusion, and coevolution of these protodomains, pointing to possible original protogenes. On protein folding itself, pseudosymmetric domains may point to a "directed" assembly of pseudosymmetric protodomains, directed by the only fact that they are tethered together in a protein chain. On function, tertiary functional sites often occur at protodomain interfaces, as they often occur at domain-domain interfaces in quaternary arrangements.First, we will briefly review some lessons learned from a previously published census of pseudosymmetry in protein domains (Myers-Turnbull, D. et al., J Mol Biol. 426:2255-2268, 2014) to introduce protodomains/protofolds. We will observe that the most abundant and diversified folds, or superfolds, in the currently known protein structure universe are indeed pseudosymmetric. Then, we will learn by example and select a few domain representatives of important pseudosymmetric folds and chief among them the immunoglobulin (Ig) fold and go over a pseudosymmetry supersecondary structure (protodomain) analysis in tertiary and quaternary structures. We will point to currently available software tools to help in identifying pseudosymmetry, delineating protodomains, and see how the study of pseudosymmetry and the underlying supersecondary structures can enrich a structural analysis. This should potentially help in protein engineering, especially in the development of biologics and immunoengineering.

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The GD box: a widespread noncontiguous supersecondary structural element.

Publications

The GD box: a widespread noncontiguous supersecondary structural element.

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