1n41: Difference between revisions

Revision as of 15:02, 21 February 2008

Crystal Structure of Annexin V K27E Mutant

OverviewOverview

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.

About this StructureAbout this Structure

1N41 is a Single protein structure of sequence from Rattus norvegicus with and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

Interfacial basic cluster in annexin V couples phospholipid binding and trimer formation on membrane surfaces., Mo Y, Campos B, Mealy TR, Commodore L, Head JF, Dedman JR, Seaton BA, J Biol Chem. 2003 Jan 24;278(4):2437-43. Epub 2002 Oct 24. PMID:12401794

Page seeded by OCA on Thu Feb 21 14:02:03 2008

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OCA

@@ Line 1: / Line 1: @@
-[[Image:1n41.gif|left|200px]]<br /><applet load="1n41" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1n41.gif|left|200px]]<br /><applet load="1n41" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1n41, resolution 2.1&Aring;" />
 '''Crystal Structure of Annexin V K27E Mutant'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-N41 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with CA and SO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1N41 OCA].
+N41 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N41 OCA].
 ==Reference==
@@ Line 15: / Line 15: @@
 [[Category: Campos, B.]]
 [[Category: Commodore, L.]]
-[[Category: Dedman, J.R.]]
+[[Category: Dedman, J R.]]
-[[Category: Head, J.F.]]
+[[Category: Head, J F.]]
-[[Category: Mealy, T.R.]]
+[[Category: Mealy, T R.]]
-[[Category: Mo, Y.D.]]
+[[Category: Mo, Y D.]]
-[[Category: Seaton, B.A.]]
+[[Category: Seaton, B A.]]
 [[Category: CA]]
 [[Category: SO4]]
@@ Line 25: / Line 25: @@
 [[Category: phospholipid membrane binding protein]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 21:56:37 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:02:03 2008''