3hhr
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3hhr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hhr OCA], [http://www.ebi.ac.uk/pdbsum/3hhr PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3hhr RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Binding of human growth hormone (hGH) to its receptor is required for regulation of normal human growth and development. Examination of the 2.8 angstrom crystal structure of the complex between the hormone and the extracellular domain of its receptor (hGHbp) showed that the complex consists of one molecule of growth hormone per two molecules of receptor. The hormone is a four-helix bundle with an unusual topology. The binding protein contains two distinct domains, similar in some respects to immunoglobulin domains. The relative orientation of these domains differs from that found between constant and variable domains in immunoglobulin Fab fragments. Both hGHbp domains contribute residues that participate in hGH binding. In the complex both receptors donate essentially the same residues to interact with the hormone, even though the two binding sites on hGH have no structural similarity. Generally, the hormone-receptor interfaces match those identified by previous mutational analyses. In addition to the hormone-receptor interfaces, there is also a substantial contact surface between the carboxyl-terminal domains of the receptors. The relative extents of the contact areas support a sequential mechanism for dimerization that may be crucial for signal transduction. | Binding of human growth hormone (hGH) to its receptor is required for regulation of normal human growth and development. Examination of the 2.8 angstrom crystal structure of the complex between the hormone and the extracellular domain of its receptor (hGHbp) showed that the complex consists of one molecule of growth hormone per two molecules of receptor. The hormone is a four-helix bundle with an unusual topology. The binding protein contains two distinct domains, similar in some respects to immunoglobulin domains. The relative orientation of these domains differs from that found between constant and variable domains in immunoglobulin Fab fragments. Both hGHbp domains contribute residues that participate in hGH binding. In the complex both receptors donate essentially the same residues to interact with the hormone, even though the two binding sites on hGH have no structural similarity. Generally, the hormone-receptor interfaces match those identified by previous mutational analyses. In addition to the hormone-receptor interfaces, there is also a substantial contact surface between the carboxyl-terminal domains of the receptors. The relative extents of the contact areas support a sequential mechanism for dimerization that may be crucial for signal transduction. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Growth hormone deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139250 139250]], Growth hormone deficiency, isolated, type IA OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139250 139250]], Growth hormone deficiency, isolated, type IB OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139250 139250]], Growth hormone deficiency, isolated, type II OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139250 139250]], Increased responsiveness to growth hormone OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600946 600946]], Kowarski syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139250 139250]], Laron dwarfism OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600946 600946]], Short stature, autosomal dominant, with normal serum growth hormone binding protein OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600946 600946]], Short stature, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139250 139250]], Short stature, idiopathic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600946 600946]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: hormone/receptor]] | [[Category: hormone/receptor]] | ||
| - | ''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 05:33:53 2008'' |
Revision as of 02:33, 31 March 2008
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| , resolution 2.8Å | |||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN GROWTH HORMONE AND EXTRACELLULAR DOMAIN OF ITS RECEPTOR: CRYSTAL STRUCTURE OF THE COMPLEX
Overview
Binding of human growth hormone (hGH) to its receptor is required for regulation of normal human growth and development. Examination of the 2.8 angstrom crystal structure of the complex between the hormone and the extracellular domain of its receptor (hGHbp) showed that the complex consists of one molecule of growth hormone per two molecules of receptor. The hormone is a four-helix bundle with an unusual topology. The binding protein contains two distinct domains, similar in some respects to immunoglobulin domains. The relative orientation of these domains differs from that found between constant and variable domains in immunoglobulin Fab fragments. Both hGHbp domains contribute residues that participate in hGH binding. In the complex both receptors donate essentially the same residues to interact with the hormone, even though the two binding sites on hGH have no structural similarity. Generally, the hormone-receptor interfaces match those identified by previous mutational analyses. In addition to the hormone-receptor interfaces, there is also a substantial contact surface between the carboxyl-terminal domains of the receptors. The relative extents of the contact areas support a sequential mechanism for dimerization that may be crucial for signal transduction.
About this Structure
3HHR is a Protein complex structure of sequences from Homo sapiens. This structure supersedes the now removed PDB entry 2HHR. The following page contains interesting information on the relation of 3HHR with [Growth Hormone]. Full crystallographic information is available from OCA.
Reference
Human growth hormone and extracellular domain of its receptor: crystal structure of the complex., de Vos AM, Ultsch M, Kossiakoff AA, Science. 1992 Jan 17;255(5042):306-12. PMID:1549776
Page seeded by OCA on Mon Mar 31 05:33:53 2008
