1N42

Crystal Structure of Annexin V R149E Mutant

Summary for 1N42

• Entry DOI: 10.2210/pdb1n42/pdb
• Descriptor: Annexin V, CALCIUM ION, SULFATE ION, ... (4 entities in total)
• Functional Keywords: calcium, phospholipid, membrane binding protein, lipid binding protein
• Biological source: Rattus norvegicus (Norway rat)
• Total number of polymer chains: 1
• Total formula weight: 36248.96

Authors

Mo, Y.D.,Campos, B.,Mealy, T.R.,Commodore, L.,Head, J.F.,Dedman, J.R.,Seaton, B.A. (deposition date: 2002-10-30, release date: 2003-02-04, Last modification date: 2024-02-14)

Primary citation

Mo, Y.D.,Campos, B.,Mealy, T.R.,Commodore, L.,Head, J.F.,Dedman, J.R.,Seaton, B.A.
Interfacial basic cluster in annexin V couples phospholipid binding and trimer formation on membrane surfaces
J.Biol.Chem., 278:2437-2443, 2003

PubMed Abstract: Annexin V is an abundant eukaryotic protein that binds phospholipid membranes in a Ca(2+)-dependent manner. In the present studies, site-directed mutagenesis was combined with x-ray crystallography and solution liposome binding assays to probe the functional role of a cluster of interfacial basic residues in annexin V. Four mutants were investigated: R23E, K27E, R61E, and R149E. All four mutants exhibited a significant reduction in adsorption to phospholipid membranes relative to the wild-type protein, and the R23E mutation was the most deleterious. Crystal structures of wild-type and mutant proteins were similar except for local changes in salt bridges involving basic cluster residues. The combined data indicate that Arg(23) is a major determinant for interfacial phospholipid binding and participates in an intermolecular salt bridge that is key for trimer formation on the membrane surface. Together, crystallographic and solution data provide evidence that the interfacial basic cluster is a locus where trimerization is synergistically coupled to membrane phospholipid binding.

PubMed: 12401794
DOI: 10.1074/jbc.M210286200

Experimental method

X-RAY DIFFRACTION (2.1 Å)