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Pcp4l1 contains an auto‐inhibitory element that prevents its IQ motif from binding to calmodulin
Author(s) -
Morgan Marc A. J.,
Morgan James I.
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07745.x
Subject(s) - calmodulin , sequence motif , biochemistry , biology , peptide sequence , binding protein , plasma protein binding , chemistry , enzyme , gene
J. Neurochem. (2012) 121 , 843–851. Abstract 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.