1g5n
From Proteopedia
(New page: 200px<br /><applet load="1g5n" size="450" color="white" frame="true" align="right" spinBox="true" caption="1g5n, resolution 1.9Å" /> '''ANNEXIN V COMPLEX WIT...) |
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| - | [[Image:1g5n.jpg|left|200px]]<br /><applet load="1g5n" size=" | + | [[Image:1g5n.jpg|left|200px]]<br /><applet load="1g5n" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1g5n, resolution 1.9Å" /> | caption="1g5n, resolution 1.9Å" /> | ||
'''ANNEXIN V COMPLEX WITH HEPARIN OLIGOSACCHARIDES'''<br /> | '''ANNEXIN V COMPLEX WITH HEPARIN OLIGOSACCHARIDES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Annexin V, an abundant anticoagulant protein, has been | + | BACKGROUND: Annexin V, an abundant anticoagulant protein, has been proposed to exert its effects by self-assembling into highly ordered arrays on phospholipid membranes to form a protective anti-thrombotic shield at the cell surface. The protein exhibits very high-affinity calcium-dependent interactions with acidic phospholipid membranes, as well as specific binding to glycosaminoglycans (GAGs) such as heparin and heparan sulfate, a major component of cell surface proteoglycans. At present, there is no structural information to elucidate this interaction or the role it may play in annexin V function at the cell surface. RESULTS: We report the 1.9 A crystal structure of annexin V in complex with heparin-derived tetrasaccharides. This structure represents the first of a heparin oligosaccharide binding to a protein where calcium ions are essential for the interaction. Two distinct GAG binding sites are situated on opposite protein surfaces. Basic residues at each site were identified from the structure and site-directed mutants were prepared. The heparin binding properties of these mutants were measured by surface plasmon resonance. The results confirm the roles of these mutated residues in heparin binding, and the kinetic and thermodynamic data define the functionally distinct character of each distal binding surface. CONCLUSION: The annexin V molecule, as it self-assembles into an organized array on the membrane surface, can bind the heparan sulfate components of cell surface proteoglycans. A novel model is presented in which proteoglycan heparan sulfate could assist in the localization of annexin V to the cell surface membrane and/or stabilization of the entire molecular assembly to promote anticoagulation. |
==About this Structure== | ==About this Structure== | ||
| - | 1G5N 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 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1G5N 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> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G5N OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Campos, B.]] | [[Category: Campos, B.]] | ||
[[Category: Capila, I.]] | [[Category: Capila, I.]] | ||
| - | [[Category: Dedman, J | + | [[Category: Dedman, J R.]] |
| - | [[Category: Heraiz, M | + | [[Category: Heraiz, M J.]] |
| - | [[Category: Linhardt, R | + | [[Category: Linhardt, R J.]] |
| - | [[Category: Mealy, T | + | [[Category: Mealy, T R.]] |
| - | [[Category: Mo, Y | + | [[Category: Mo, Y D.]] |
| - | [[Category: Seaton, B | + | [[Category: Seaton, B A.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: calcium]] | [[Category: calcium]] | ||
| Line 28: | Line 28: | ||
[[Category: membrane binding]] | [[Category: membrane binding]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:46:26 2008'' |
Revision as of 10:46, 21 February 2008
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ANNEXIN V COMPLEX WITH HEPARIN OLIGOSACCHARIDES
Overview
BACKGROUND: Annexin V, an abundant anticoagulant protein, has been proposed to exert its effects by self-assembling into highly ordered arrays on phospholipid membranes to form a protective anti-thrombotic shield at the cell surface. The protein exhibits very high-affinity calcium-dependent interactions with acidic phospholipid membranes, as well as specific binding to glycosaminoglycans (GAGs) such as heparin and heparan sulfate, a major component of cell surface proteoglycans. At present, there is no structural information to elucidate this interaction or the role it may play in annexin V function at the cell surface. RESULTS: We report the 1.9 A crystal structure of annexin V in complex with heparin-derived tetrasaccharides. This structure represents the first of a heparin oligosaccharide binding to a protein where calcium ions are essential for the interaction. Two distinct GAG binding sites are situated on opposite protein surfaces. Basic residues at each site were identified from the structure and site-directed mutants were prepared. The heparin binding properties of these mutants were measured by surface plasmon resonance. The results confirm the roles of these mutated residues in heparin binding, and the kinetic and thermodynamic data define the functionally distinct character of each distal binding surface. CONCLUSION: The annexin V molecule, as it self-assembles into an organized array on the membrane surface, can bind the heparan sulfate components of cell surface proteoglycans. A novel model is presented in which proteoglycan heparan sulfate could assist in the localization of annexin V to the cell surface membrane and/or stabilization of the entire molecular assembly to promote anticoagulation.
About this Structure
1G5N is a Single protein structure of sequence from Rattus norvegicus with as ligand. Full crystallographic information is available from OCA.
Reference
Annexin V--heparin oligosaccharide complex suggests heparan sulfate--mediated assembly on cell surfaces., Capila I, Hernaiz MJ, Mo YD, Mealy TR, Campos B, Dedman JR, Linhardt RJ, Seaton BA, Structure. 2001 Jan 10;9(1):57-64. PMID:11342135
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