Three-dimensional domain swapping in p13suc1 occurs in the unfolded state and is controlled by conserved proline residues.

Frederic Rousseau, Joost Schymkowitz, Hannah WILKINSON, L.s. Itzhaki

Research output: Contribution to journalArticlepeer-review

182 Citations (Scopus)

Abstract

p13suc1 has two native states, a monomer and a domain-swapped dimer. We show that their folding pathways are connected by the denatured state, which introduces a kinetic barrier between monomer and dimer ender native conditions. The barrier is lowered under conditions that speed up unfolding, thereby allowing, to our knowledge for the first time, a quantitative dissection of the energetics of domain swapping. The monomer-dimer equilibrium is controlled by two conserved prolines in the hinge loop that connects the exchanging domains. these two residues exploit backbone strain to specifically direct dimer formation while preventing higher-order oligomerization. Thus, the loop acts as a loaded molecular spring that releases tension in the monomer by adopting its alternative conformation in the dimer. There is an excellent correlation between domain swapping and aggregation, suggesting they share a common mechanism. These insights have allowed us to redesign the domain-swapping propensity of suc1 from a fully monomeric to a fully dimeric protein.
Original languageEnglish
Pages (from-to)5596-5601
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number10
Publication statusPublished - 8 May 2001

Bibliographical note

Proc.Nat.Acad.Sci.USA,pag.5596-601,Vol.98,2001

Keywords

  • p13

Fingerprint

Dive into the research topics of 'Three-dimensional domain swapping in p13suc1 occurs in the unfolded state and is controlled by conserved proline residues.'. Together they form a unique fingerprint.

Cite this