2n77

Publication Abstract from PubMed

PEP-19 is a small protein that increases the rates of Ca2+ binding to the C-domain of calmodulin (CaM) by an unknown mechanism. Although an IQ motif promotes binding to CaM, an acidic sequence in PEP-19 is required to modulate Ca2+ binding and to sensitize HeLa cells to ATP-induced Ca2+ release. Here, we report the NMR solution structure of a complex between PEP-19 and the C-domain of apo CaM. The acidic sequence of PEP-19 associates between helices E and F of CaM via hydrophobic interactions. This allows the acidic side chains in PEP-19 to extend toward the solvent and form a negatively charged surface that resembles a catcher's mitt near Ca2+ binding loop III of CaM. The topology and gradients of negative electrostatic surface potential support a mechanism by which PEP-19 increases the rate of Ca2+ binding to the C-domain of CaM by 'catching' and electrostatically steering Ca2+ to site III.

PEP-19 modulates calcium binding to calmodulin by electrostatic steering.,Wang X, Putkey JA Nat Commun. 2016 Nov 23;7:13583. doi: 10.1038/ncomms13583. PMID:27876793^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.