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Helix packing in proteins: Prediction and energetic analysis of dimeric, trimeric, and tetrameric GCN4 coiled coil structures
Author(s) -
Delano Warren L.,
Brünger Axel T.
Publication year - 1994
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/prot.340200202
Subject(s) - dimer , coiled coil , crystallography , tetramer , trimer , chemistry , leucine zipper , helix (gastropod) , protein structure , side chain , crystal structure , stereochemistry , peptide sequence , polymer , biology , biochemistry , ecology , organic chemistry , snail , gene , enzyme
A simulated annealing method for atomic resolution structure prediction of α‐helical coiled coil proteins is described which draws upon knowledge of the oligomerization state, the helix directionality, and the properties of heptad repeat sequences. Unknown structural parameters, such as the coiled coil twist angle and the side chain conformations, are heavily sampled while allowing for flexibility in the helix backbone geometry. Structures of the wild‐type GCN4 dimer [O'Shea et al., Science 254:539–544, 1991] and a mutant tetramer [Harbury et al., Science 292:1401–1407, 1993] have been generated and compared with the X‐ray crystal structures. The wild‐type dimer model has a root mean square coordinate deviation from the crystal structure of 0.73 Å for nonhydrogen atoms in the dimerization interface. Structures of a mutant dimer and a mutant trimer have been predicted. Packing energetics were analyzed for core leucine and isoleucine side chains in dimeric and tetrameric coiled coils. Strong packing preferences were found in the dimers but not in the tetramers. Thus, packing in the dimer may be responsible for the switch from a two‐stranded to a four‐stranded coiled coil caused by the GCN4 leucine zipper mutations. © 1994 Wiley‐Liss, Inc.