Document Detail


Extended knobs-into-holes packing in classical and complex coiled-coil assemblies.
MedLine Citation:
PMID:  14643203     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This year marks the 50th anniversary of Crick's seminal paper on the packing of alpha-helices into coiled-coil structures. The central tenet of Crick's work is the interdigitation of side chains, which directs the helix-helix interactions; so called knobs-into-holes packing. Subsequent determinations of coiled-coil-protein sequences and structures confirmed the key features of Crick's model and established it as a fundamental concept in structural biology. Recently, we developed a program, SOCKET, to recognise knobs-into-holes packing in protein structures, which we applied to the Protein Data Bank to compile a database of coiled-coil structures. In addition to classic structures, the database reveals 4-helix bundles and larger helical assemblies. Here, we describe how the more-complex structures can be understood by extending Crick's principles for classic coiled coils. In the simplest case, each helix of a 2-stranded structure contributes a single seam of (core) knobs-into-holes to the helical interface. 3-, 4-, and 5-Stranded structures, however, are best considered as rings of helices with cycles of knobs-into-holes. These higher-order oligomers make additional (peripheral) knobs-into-holes that broaden the helical contacts. Combinations of core and peripheral knobs may be assigned to different sequence repeats offset within the same helix. Such multiple repeats lead to multi-faceted helices, which explain structures above dimers. For instance, coiled-coil oligomer state correlates with the offset of the different repeats along a sequence. In addition, certain multi-helix assemblies can be considered as conjoined coiled coils in which multi-faceted helices participate in more than one coiled-coil motif.
Authors:
John Walshaw; Derek N Woolfson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of structural biology     Volume:  144     ISSN:  1047-8477     ISO Abbreviation:  J. Struct. Biol.     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2003-12-03     Completed Date:  2004-07-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9011206     Medline TA:  J Struct Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  349-61     Citation Subset:  IM    
Affiliation:
Centre for Biomolecular Design and Drug Development, John Maynard-Smith Building, School of Life Sciences, University of Sussex, Falmer BN1 9QG, UK.
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MeSH Terms
Descriptor/Qualifier:
Algorithms
Amino Acid Motifs
Models, Molecular
Nucleic Acid Conformation*
Protein Binding
Protein Conformation
Protein Structure, Secondary
Software

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