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Folding and self-assembly of a small protein complex.

ABSTRACT: The synthetic homotetrameric ??? (BBAT1) protein possesses a stable quaternary structure with a ??? fold. Because of its small size (a total of 84 residues), the homotetramer is an excellent model system with which to study the self-assembly and protein-protein interactions. We find from replica exchange molecular dynamics simulations with the coarse-grain UNRES force field that the folding and association pathway consists of three well-separated steps, where that association to a tetramer precedes and facilitates folding of the four chains. At room temperature the tetramer exists in an ensemble of diverse structures. The crystal structure becomes energetically favored only when the molecule is put in a dense and crystal-like environment. The observed picture of folding promoted by association may mirror the mechanism according to which intrinsically unfolded proteins assume their functional structure.

SUBMITTER: Sieradzan AK

PROVIDER: S-EPMC3771543 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Folding and self-assembly of a small protein complex.

Sieradzan Adam K AK Liwo Adam A Hansmann Ulrich H E UH

Journal of chemical theory and computation 20120901 9

The synthetic homotetrameric ββα (BBAT1) protein possesses a stable quaternary structure with a ββα fold. Because of its small size (a total of 84 residues), the homotetramer is an excellent model system with which to study the self-assembly and protein-protein interactions. We find from replica exchange molecular dynamics simulations with the coarse-grain UNRES force field that the folding and association pathway consists of three well-separated steps, where that association to a tetramer prece ...[more]

PMID: 24039552

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