| First Author | Morgan MA | Year | 2012 |
| Journal | J Neurochem | Volume | 121 |
| Issue | 6 | Pages | 843-51 |
| PubMed ID | 22458599 | Mgi Jnum | J:185441 |
| Mgi Id | MGI:5428792 | Doi | 10.1111/j.1471-4159.2012.07745.x |
| Citation | Morgan MA, et al. (2012) Pcp4l1 contains an auto-inhibitory element that prevents its IQ motif from binding to calmodulin. J Neurochem 121(6):843-51 |
| abstractText | Purkinje cell protein 4-like 1 (Pcp4l1) is a small neuronal IQ motif protein closely related to the calmodulin-binding protein Pcp4/PEP-19. PEP-19 interacts with calmodulin via its IQ motif to inhibit calmodulin-dependent enzymes and we hypothesized Pcp4l1 would have similar properties. Surprisingly, full-length Pcp4l1 does not interact with calmodulin in yeast two-hybrid or pulldown experiments yet a synthetic peptide constituting only the IQ motif of Pcp4l1 binds calmodulin and inhibits calmodulin-dependent kinase II. A nine-residue glutamic acid-rich sequence in Pcp4l1 confers these unexpected properties. This element lies outside the IQ motif and its deletion or exchange with the homologous region of PEP-19 restores calmodulin binding. Conversion of a single isoleucine (Ile36) within this motif to phenylalanine, the residue present in PEP-19, imparts calmodulin binding onto Pcp4l1. Moreover, only aromatic amino acid substitutions at position 36 in Pcp4l1 allow binding. Thus, despite their sequence similarities PEP-19 and Pcp4l1 have distinct properties with the latter harboring an element that can functionally suppress an IQ motif. We speculate Pcp4l1 may be a latent calmodulin inhibitor regulated by post-translational modification and/or co-factor interactions. |
