Abstract
Pin1 is a peptidyl-prolyl isomerase responsible for isomerizing phosphorylated S/T-P motifs. Pin1 has two domains that each have a distinct ligand binding site, but only its PPIase domain has catalytic activity. Vast evidence supports interdomain allostery of Pin1, with binding of a ligand to its regulatory WW domain impacting activity in the PPIase domain. Many diverse studies have made mutations in Pin1 in order to elucidate interactions that are responsible for ligand binding, isomerase activity, and interdomain allostery. Here, we summarize these mutations and their impact on Pin1′s structure and function.
Highlights
Pin1, or Protein interacting with Never-in-Mitosis (NIMA) 1, is a phosphorylation-dependent peptidyl-prolyl cis-trans isomerase (PPIase) [1]
Unlike the mutations studied in the WW domain involving full-length Pin1, mutations evaluated in the PPIase domain were from a mixture of studies with either the isolated PPIase domain or full-length Pin1
It is surprising how the 40∆NSSSG/W34A/R17A mutant had slightly higher activity than 40∆NSSSG, but this discrepancy was not addressed [9]. Another mutation investigated on the isolated PPIase domain was S138A, which is proposed to mimic the structural impact of the WW domain ID contact
Summary
Protein interacting with Never-in-Mitosis (NIMA) 1, is a phosphorylation-dependent peptidyl-prolyl cis-trans isomerase (PPIase) [1]. Ligand binding and mutation studies suggest that the WW domain allosterically regulates the activity of the PPIase domain. Pin isincapable of binding and isomerizing many different substrates, all peptide ligandsthat discussed this review. With the commonality of a pS/T-P motif (Figure 1) Despite this shared motif, not all substrates cause the same structural changes to Pin upon binding. Peptides with sequences WFYpSPR, FFpSPR, and YpSPTpSPS cause a shift to a more compact state of Pin1 [6]. This ligand-dependent shift in interdomain equilibrium triggers different responses in PPIase dynamics and catalytic activity. A comprehensive review of the structure and function of Pin summarizes the current knowledge in the field [33]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
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.
