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J Am Chem Soc. 2013 Sep 4;135(35):12980-3. doi: 10.1021/ja406958k. Epub 2013 Aug 21.

Cd2+ as a Ca2+ surrogate in protein-membrane interactions: isostructural but not isofunctional.

Author information

1
Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, United States.

Abstract

Due to its favorable spectroscopic properties, Cd(2+) is frequently used as a probe of Ca(2+) sites in proteins. We investigate the ability of Cd(2+) to act as a structural and functional surrogate of Ca(2+) in protein-membrane interactions. C2 domain from protein kinase Cα (C2α) was chosen as a paradigm for the Ca(2+)-dependent phosphatidylserine-binding peripheral membrane domains. We identified the Cd(2+)-binding sites of C2α using NMR spectroscopy, determined the 1.6 Å crystal structure of Cd(2+)-bound C2α, and characterized metal-ion-dependent interactions between C2α and phospholipid membranes using fluorescence spectroscopy and ultracentrifugation experiments. We show that Cd(2+) forms a tight complex with the membrane-binding loops of C2α but is unable to support its membrane-binding function. This is in sharp contrast with Pb(2+), which is almost as effective as Ca(2+) in driving the C2α-membrane association process. Our results provide the first direct evidence for the specific role of divalent metal ions in mediating protein-membrane interactions, have important implications for metal substitution studies in proteins, and illustrate the potential diversity of functional responses caused by toxic metal ions.

PMID:
23937054
PMCID:
PMC4749353
DOI:
10.1021/ja406958k
[Indexed for MEDLINE]
Free PMC Article

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