Topological determinants of protein domain swapping

Feng Ding, Kirk C. Prutzman, Sharon L. Campbell, Nikolay V. Dokholyan

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Protein domain swapping has been repeatedly observed in a variety of proteins and is believed to result from destabilization due to mutations or changes in environment. Based on results from our studies and others, we propose that structures of the domain-swapped proteins are mainly determined by their native topologies. We performed molecular dynamics simulations of seven different proteins, known to undergo domain swapping experimentally, under mildly denaturing conditions and found in all cases that the domain-swapped structures can be recapitulated by using protein topology in a simple protein model. Our studies further indicated that, in many cases, domain swapping occurs at positions around which the protein tends to unfold prior to complete unfolding. This, in turn, enabled prediction of protein structural elements that are responsible for domain swapping. In particular, two distinct domain-swapped dimer conformations of the focal adhesion targeting domain of focal adhesion kinase were predicted computationally and were supported experimentally by data obtained from NMR analyses.

Original languageEnglish (US)
Pages (from-to)5-14
Number of pages10
JournalStructure
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2006

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Proteins
Focal Adhesion Protein-Tyrosine Kinases
Focal Adhesions
Molecular Dynamics Simulation
Protein Domains
Mutation
Protein Structural Elements

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Cite this

Ding, Feng ; Prutzman, Kirk C. ; Campbell, Sharon L. ; Dokholyan, Nikolay V. / Topological determinants of protein domain swapping. In: Structure. 2006 ; Vol. 14, No. 1. pp. 5-14.
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Topological determinants of protein domain swapping. / Ding, Feng; Prutzman, Kirk C.; Campbell, Sharon L.; Dokholyan, Nikolay V.

In: Structure, Vol. 14, No. 1, 01.01.2006, p. 5-14.

Research output: Contribution to journalArticle

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