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Calcineurin regulatory subunit B is a unique calcium sensor that regulates calcineurin in both calcium‐dependent and calcium‐independent manner
Author(s) -
Li Jing,
Jia ZhiGuang,
Zhou WenChang,
Wei Qun
Publication year - 2009
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22474
Subject(s) - calcineurin , calmodulin , protein subunit , chemistry , calcium , phosphatase , calcium binding protein , biochemistry , circular dichroism , biophysics , ef hand , biology , enzyme , gene , medicine , surgery , organic chemistry , transplantation
Calcineurin subunit B (CNB), a regulatory subunit of calcineurin, is a member of EF‐hand calcium (Ca 2+ )‐binding protein superfamily. In this study, we performed phosphatase activity, pull‐down, and circular dichroism analyses, which shows Ca 2+ ‐free CNB (apo‐CNB) is able to bind CNA (Calcineurin subunit A) and regulate its phosphatase activity, albeit to a lesser extent than Ca 2+ ‐saturated CNB (holo‐CNB). This is supported by subsequent molecular dynamics (MD) simulations which aimed to examine calcium‐induced conformational changes of CNB, using both holo‐CNB and apo‐CNB. Based on the trajectories of MD, we found that there were no drastic changes between holo‐CNB and apo‐CNB. The modest differences seen are mainly reflected in the interhelical angles of the four EF‐hand motifs and solvent accessible surface area of the hydrophobic groove which is responsible for CNA binding. Interestingly, this hydrophobic groove was largely retained in both holo‐CNB and apo‐CNB. Comparative analyses show that the calcium‐induced conformational change in CNB is remarkably different from that of the two prototypical EF‐hand calcium‐binding proteins, namely, calmodulin and recoverin. This is the first time that CNB is shown to activate CNA in the absence of Ca 2+ . Proteins 2009. © 2009 Wiley‐Liss, Inc.