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Molecular modeling of vimentin filament assembly
Author(s) -
Downing Donald Talbot
Publication year - 1996
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(199612)26:4<472::aid-prot8>3.0.co;2-d
Subject(s) - tetramer , crystallography , chemistry , side chain , folding (dsp implementation) , protein filament , helix (gastropod) , trimer , hydrophobic effect , oligomer , chemical physics , biophysics , dimer , polymer chemistry , polymer , organic chemistry , ecology , biochemistry , snail , electrical engineering , biology , enzyme , engineering
Intermediate‐filament forming proteins are known to form rod‐shaped dimers that are calculated to be 45 nm in length. Molecular modeling indicates that the dimerization is promoted by interchain hydrophobic interactions between sections of α helix β and helix. Further aggregation involves the formation of tetramers in which two dimers are anti‐parallel and staggered to two characteristic degrees of overlap. Modeling indicated that the degrees of stagger are dictated by the association of sections of α helix in 4‐chain bundles, in which hydrophobic side chains are sequestered from contact with water. The staggered arrangement of two dimers produces a tetramer having sections of 2‐chain rod in which hydrophobic side chains are exposed to water. Extension of the tetramer to form protofilaments may be driven by associations with the 2‐chain regions that reduce aqueous exposure of the hydrophobic side chains. Exposure of hydrophobic groups may be reduced by the 2‐chain regions folding back upon themselves so that the entire tetramer becomes a 4‐chain conformation. This prediction is in line with electron microscope data showing that mixtures of the lower oligomers contain rods of uniform thickness ranging upwards from 45 nm in a series having incremental increases in length. Data from previous chemical crosslinking studies support this model and also the idea that the completed intermediate filaments each consist of seven 4‐chain protofilaments. Proteins 26:472–478 © 1996 Wiley‐Liss, Inc.