AI Article Synopsis
- - Inhibitory serpins are specialized proteins that change shape to effectively trap target peptidases, largely due to interactions from their reactive center loop during initial binding.
- - Studies show that these serpins have multiple contact points that affect how well they recognize and bind to peptidases, and improper folding can result in problematic structures known as domain-swapped multimers.
- - Recent research indicates that the structure of serpins has evolved beyond just inhibition to also play roles in non-inhibitory functions, like binding hormones.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2915666 | PMC |
| http://dx.doi.org/10.1074/jbc.R110.141408 | DOI Listing |
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