PDBsum entry 4l1l

Transferase

PDB id: 4l1l

Contents

Protein chain

138 a.a.

Ligands

SO4 ×5

Metals

_CD ×6

Waters ×141

References listed in PDB file

Key reference

• Title: Cd2+ as a ca2+ surrogate in protein-Membrane interactions: isostructural but not isofunctional.
• Authors: K.A.Morales, Y.Yang, Z.Long, P.Li, A.B.Taylor, P.J.Hart, T.I.Igumenova.
• Ref.: J Am Chem Soc, 2013, 135, 12980-12983. [DOI no: 10.1021/ja406958k]
• PubMed id: 23937054

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.