Socket: a program for identifying and analysing coiled-coil motifs within protein structures.
The coiled coil is arguably the simplest protein-structure motif and probably the most ubiquitous facilitator of protein-protein interactions. Coiled coils comprise two or more alpha-helices that wind around each other to form "supercoils". The hallmark of most coiled coils is a regular sequence pattern known as the heptad repeat. Despite this apparent simplicity and relatedness at the sequence level, coiled coils display a considerable degree of structural diversity: the helices may be arranged parallel or anti-parallel and may form a variety of oligomer states. To aid studies of coiled coils, we developed SOCKET, a computer program to identify these motifs automatically in protein structures. We used SOCKET to gather a set of unambiguous coiled-coil structures from the RCSB Protein Data Bank. Rather than searching for sequence features, the algorithm recognises the characteristic knobs-into-holes side-chain packing of coiled coils; this proved to be straightforward to implement and was able to distinguish coiled coils from the great majority of helix-helix packing arrangements observed in globular domains. SOCKET unambiguously defines coiled-coil helix boundaries, oligomerisation states and helix orientations, and also assigns heptad registers. Structures retrieved from the Protein Data Bank included parallel and anti-parallel variants of two, three and four-stranded coiled coils, one example of a parallel pentamer and a small number of structures that extend the classical description of a coiled coil. We anticipate that our structural database and the associated sequence data that we have gathered will be of use in identifying principles for coiled-coil assembly, prediction and design. To illustrate this we give examples of sequence and structural analyses of the structures that are possible using the new data bases, and we present amino acid profiles for the heptad repeats of different motifs.
Walshaw
J
J
Centre for Biomolecular Design and Drug Development, School of Biological Sciences, University of Sussex, Falmer, East Sussex, BN1 9QG, UK.
Woolfson
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D000465:Algorithms; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods; D004268:DNA-Binding Proteins; D019992:Databases as Topic; D019281:Dimerization; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D020407:Internet; D016350:Leucine Zippers; D008958:Models, Molecular; D011485:Protein Binding; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D012984:Software; D013329:Structure-Activity Relationship
D000596:Amino Acids; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases