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Domain swapping is a consequence of minimal frustration.

ABSTRACT: The same energy landscape principles associated with the folding of proteins into their monomeric conformations should also describe how these proteins oligomerize into domain-swapped conformations. We tested this hypothesis by using a simplified model for the epidermal growth factor receptor pathway substrate 8 src homology 3 domain protein, both of whose monomeric and domain-swapped structures have been solved. The model, which we call the symmetrized G?-type model, incorporates only information regarding the monomeric conformation in an energy function for the dimer to predict the domain-swapped conformation. A striking preference for the correct domain-swapped structure was observed, indicating that overall monomer topology is a main determinant of the structure of domain-swapped dimers. Furthermore, we explore the free energy surface for domain swapping by using our model to characterize the mechanism of oligomerization.

SUBMITTER: Yang S

PROVIDER: S-EPMC518834 | biostudies-literature | 2004 Sep

REPOSITORIES: biostudies-literature

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Domain swapping is a consequence of minimal frustration.

Yang Sichun S Cho Samuel S SS Levy Yaakov Y Cheung Margaret S MS Levine Herbert H Wolynes Peter G PG Onuchic José N JN

Proceedings of the National Academy of Sciences of the United States of America 20040910 38

The same energy landscape principles associated with the folding of proteins into their monomeric conformations should also describe how these proteins oligomerize into domain-swapped conformations. We tested this hypothesis by using a simplified model for the epidermal growth factor receptor pathway substrate 8 src homology 3 domain protein, both of whose monomeric and domain-swapped structures have been solved. The model, which we call the symmetrized Gō-type model, incorporates only informati ...[more]

PMID: 15361578

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