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J Biol Chem. 2010 Aug 6;285(32):24307-12. doi: 10.1074/jbc.R110.141408. Epub 2010 May 24.

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

Author information

1
From the Department of Biochemistry and Molecular Biology and ARC Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, Clayton, Victoria 3800, Australia. james.whisstock@monash.edu.au

Abstract

Inhibitory serpins are metastable proteins that undergo a substantial conformational rearrangement to covalently trap target peptidases. The serpin reactive center 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.

PMID:
20498368
PMCID:
PMC2915666
DOI:
10.1074/jbc.R110.141408
[Indexed for MEDLINE]
Free PMC Article

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