Serpins flex their muscle: II. Structural insights into target peptidase recognition, polymerization, and transport functions

James C Whisstock, Gary A Silverman, Phillip Ian Bird, Stephen Paul Bottomley, Dion Kaiserman, Cliff J Luke, Stephen C Pak, Jean -Marc Reichhart, James A Huntington

Research output: Contribution to journalArticleResearchpeer-review

92 Citations (Scopus)


Inhibitory serpins are metastable proteins that undergo a substantial a conformational rearrangement to covalently trap target peptidases. The serpin reactive centre loop contributes a majority of the interactions that serpins make during the initial binding to target peptidases. However, structural studies on serpin-peptidase complexes reveal a broader set of contacts on the scaffold of inhibitory serpins that have substantial influence on guiding peptidase recognition. Structural and biophysical studies also reveal how aberrant serpin folding can lead to the formation of domain-swapped serpin multimers rather than the monomeric metastable state. Serpin domain swapping may therefore underlie the polymerization events characteristic of the serpinopathies. Finally, recent structural studies reveal how the serpin fold has been adapted for non-inhibitory functions such as hormone binding.
Original languageEnglish
Pages (from-to)24307 - 24312
Number of pages6
JournalJournal of Biological Chemistry
Issue number32
Publication statusPublished - 2010

Cite this