2hp4: Difference between revisions
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|PDB= 2hp4 |SIZE=350|CAPTION= <scene name='initialview01'>2hp4</scene>, resolution 2.10Å | |PDB= 2hp4 |SIZE=350|CAPTION= <scene name='initialview01'>2hp4</scene>, resolution 2.10Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hp4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hp4 OCA], [http://www.ebi.ac.uk/pdbsum/2hp4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2hp4 RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
Human CD8 is a T cell coreceptor, which binds to pHLA I and plays a pivotal role in the activation of cytotoxic T lymphocytes. Soluble recombinant CD8 alphaalpha has been shown to antagonize T cell activation, both in vitro and in vivo. However, because of a very low affinity for pHLA I, high concentrations of soluble CD8 alphaalpha are required for efficient inhibition. Based upon our knowledge of the wild-type CD8/pHLA I structure, we have designed and produced a mutated form of soluble CD8 alphaalpha that binds to pHLA I with approximately fourfold higher affinity. We have characterized the binding of the high affinity CD8 mutant using surface plasmon resonance and determined its structure at 2.1 A resolution using X-ray crystallography. The analysis of this structure suggests that the higher affinity is achieved by providing a larger side chain that allows for an optimal contact to be made between the HLA alpha3 loop and the mutated CDR-like loops of CD8. | Human CD8 is a T cell coreceptor, which binds to pHLA I and plays a pivotal role in the activation of cytotoxic T lymphocytes. Soluble recombinant CD8 alphaalpha has been shown to antagonize T cell activation, both in vitro and in vivo. However, because of a very low affinity for pHLA I, high concentrations of soluble CD8 alphaalpha are required for efficient inhibition. Based upon our knowledge of the wild-type CD8/pHLA I structure, we have designed and produced a mutated form of soluble CD8 alphaalpha that binds to pHLA I with approximately fourfold higher affinity. We have characterized the binding of the high affinity CD8 mutant using surface plasmon resonance and determined its structure at 2.1 A resolution using X-ray crystallography. The analysis of this structure suggests that the higher affinity is achieved by providing a larger side chain that allows for an optimal contact to be made between the HLA alpha3 loop and the mutated CDR-like loops of CD8. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Jakobsen, B K.]] | [[Category: Jakobsen, B K.]] | ||
[[Category: Rizkallah, P J.]] | [[Category: Rizkallah, P J.]] | ||
[[Category: cd8]] | [[Category: cd8]] | ||
[[Category: co-receptor]] | [[Category: co-receptor]] | ||
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[[Category: soluble protein]] | [[Category: soluble protein]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:33:22 2008'' | ||
