2hp4
From Proteopedia
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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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known disease associated with this structure: Megakaryoblastic leukemia, acute OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606078 606078]] | ||
==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: GOL]] | ||
| - | [[Category: SO4]] | ||
[[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'' |
Revision as of 00:33, 31 March 2008
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| , resolution 2.10Å | |||||||
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| Ligands: | , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Computational design and crystal structure of an enhanced affinity mutant human CD8-alpha-alpha co-receptor
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.
About this Structure
2HP4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Computational design and crystal structure of an enhanced affinity mutant human CD8 alphaalpha coreceptor., Cole DK, Rizkallah PJ, Boulter JM, Sami M, Vuidepot AL, Glick M, Gao F, Bell JI, Jakobsen BK, Gao GF, Proteins. 2007 Apr 1;67(1):65-74. PMID:17243170
Page seeded by OCA on Mon Mar 31 03:33:22 2008
