2CM6

crystal structure of the C2B domain of rabphilin3A

Summary for 2CM6

• Entry DOI: 10.2210/pdb2cm6/pdb
• Related: 1ZBD 2CHD 2CM5 3RPB
• Descriptor: RABPHILIN-3A, CALCIUM ION, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: protein transport, zinc-finger, rabphilin3a, ca2+ binding, metal-binding, synaptic exocytosis, c2a-c2b linker fragment, c2b, zinc, synapse, c2 domain, transport
• Biological source: RATTUS NORVEGICUS (RAT)
• Cellular location: Cell junction, synapse (By similarity): P47709
• Total number of polymer chains: 2
• Total formula weight: 38470.91

Authors

Schlicker, C.,Montaville, P.,Sheldrick, G.M.,Becker, S. (deposition date: 2006-05-04, release date: 2006-12-04, Last modification date: 2023-12-13)

Primary citation

Montaville, P.,Schlicker, C.,Leonov, A.,Zweckstetter, M.,Sheldrick, G.M.,Becker, S.
The C2A-C2B Linker Defines the High Affinity Ca2+ Binding Mode of Rabphilin-3A.
J.Biol.Chem., 282:5015-, 2007

PubMed Abstract: The Ca(2+) binding properties of C2 domains are essential for the function of their host proteins. We present here the first crystal structures showing an unexpected Ca(2+) binding mode of the C2B domain of rabphilin-3A in atomic detail. Acidic residues from the linker region between the C2A and C2B domains of rabphilin-3A interact with the Ca(2+)-binding region of the C2B domain. Because of these interactions, the coordination sphere of the two bound Ca(2+) ions is almost complete. Mutation of these acidic residues to alanine resulted in a 10-fold decrease in the intrinsic Ca(2+) binding affinity of the C2B domain. Using NMR spectroscopy, we show that this interaction occurred only in the Ca(2+)-bound state of the C2B domain. In addition, this Ca(2+) binding mode was maintained in the C2 domain tandem fragment. In NMR-based liposome binding assays, the linker was not released upon phospholipid binding. Therefore, this unprecedented Ca(2+) binding mode not only shows how a C2 domain increases its intrinsic Ca(2+) affinity, but also provides the structural base for an atypical protein-Ca(2+)-phospholipid binding mode of rabphilin-3A.

PubMed: 17166855
DOI: 10.1074/JBC.M606746200

Experimental method

X-RAY DIFFRACTION (1.85 Å)