Abstract
Pin1 is a two-domain peptidyl-prolyl isomerase (PPIase) associated with neurodegeneration and tumorigenesis. The two domains, a WW and a PPIase domain, are connected by a flexible linker, making Pin1 adopt various conformations ranging from compact to extended, wherein Pin1 exhibits different extents of interdomain contact. Previous studies have shown that weakening interdomain contact increases the isomerase activity of Pin1. Here, we propose an NMR chemical shift correlation-analysis-based method that will be general for two-domain proteins to gauge two-state populations of Pin1, and we report a linker-modified mutant of Pin1 with enhanced interdomain contact and increased isomerase activity, with the latter suggesting an uncorrelated effect of interdomain contact on isomerase activity. Thus, although bindings of different substrates in the WW domain impose opposite effects on interdomain contact, in both cases, it may promote isomerization, implying cooperativity between substrate binding in the WW domain and isomerization in the PPIase domain.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
