4L1L

Rat PKC C2 domain bound to CD

Summary for 4L1L

• Entry DOI: 10.2210/pdb4l1l/pdb
• Descriptor: Protein kinase C alpha type, SULFATE ION, CADMIUM ION, ... (4 entities in total)
• Functional Keywords: protein kinase pkc, transferase
• Biological source: Rattus norvegicus (rat)
• Cellular location: Cytoplasm: P05696
• Total number of polymer chains: 1
• Total formula weight: 17395.23

Authors

Morales, K.M.,Yang, Y.,Long, Z.,Li, P.,Taylor, A.B.,Hart, P.J.,Igumenova, T.I. (deposition date: 2013-06-03, release date: 2013-08-28, Last modification date: 2024-02-28)

Primary citation

Morales, K.A.,Yang, Y.,Long, Z.,Li, P.,Taylor, A.B.,Hart, P.J.,Igumenova, T.I.
Cd(2+) as a ca(2+) surrogate in protein-membrane interactions: isostructural but not isofunctional.
J.Am.Chem.Soc., 135:12980-12983, 2013

PubMed 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.

PubMed: 23937054
DOI: 10.1021/ja406958k

Experimental method

X-RAY DIFFRACTION (1.6 Å)