View source for 1axi


==STRUCTURAL PLASTICITY AT THE HGH:HGHBP INTERFACE==
<StructureSection load='1axi' size='340' side='right'caption='[[1axi]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1axi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AXI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1axi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1axi OCA], [https://pdbe.org/1axi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1axi RCSB], [https://www.ebi.ac.uk/pdbsum/1axi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1axi ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SOMA_HUMAN SOMA_HUMAN] Defects in GH1 are a cause of growth hormone deficiency isolated type 1A (IGHD1A) [MIM:[https://omim.org/entry/262400 262400]; also known as pituitary dwarfism I. IGHD1A is an autosomal recessive deficiency of GH which causes short stature. IGHD1A patients have an absence of GH with severe dwarfism and often develop anti-GH antibodies when given exogenous GH.<ref>PMID:8364549</ref>   Defects in GH1 are a cause of growth hormone deficiency isolated type 1B (IGHD1B) [MIM:[https://omim.org/entry/612781 612781]; also known as dwarfism of Sindh. IGHD1B is an autosomal recessive deficiency of GH which causes short stature. IGHD1B patients have low but detectable levels of GH. Dwarfism is less severe than in IGHD1A and patients usually respond well to exogenous GH.  Defects in GH1 are the cause of Kowarski syndrome (KWKS) [MIM:[https://omim.org/entry/262650 262650]; also known as pituitary dwarfism VI.<ref>PMID:8552145</ref> <ref>PMID:9276733</ref> <ref>PMID:17519310</ref>   Defects in GH1 are a cause of growth hormone deficiency isolated type 2 (IGHD2) [MIM:[https://omim.org/entry/173100 173100]. IGHD2 is an autosomal dominant deficiency of GH which causes short stature. Clinical severity is variable. Patients have a positive response and immunologic tolerance to growth hormone therapy.
== Function ==
[https://www.uniprot.org/uniprot/SOMA_HUMAN SOMA_HUMAN] Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ax/1axi_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1axi ConSurf].
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== Publication Abstract from PubMed ==
Remodeling of the interface between human growth hormone (hGH) and the extracellular domain of its receptor was studied by deleting a critical tryptophan residue (at position 104) in the receptor, creating a large cavity, and selecting a pentamutant of hGH by phage display that fills the cavity and largely restores binding affinity. A 2.1 A resolution x-ray structure of the mutant complex showed that the receptor cavity was filled by selected hydrophobic mutations of hGH. Large structural rearrangements occurred in the interface at sites that were distant from the mutations. Such plasticity may be a means for protein-protein interfaces to adapt to mutations as they coevolve.

Structural plasticity in a remodeled protein-protein interface.,Atwell S, Ultsch M, De Vos AM, Wells JA Science. 1997 Nov 7;278(5340):1125-8. PMID:9353194<ref>PMID:9353194</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1axi" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cation-pi interactions|Cation-pi interactions]]
*[[Human growth hormone|Human growth hormone]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Atwell S]]
[[Category: De Vos AM]]
[[Category: Ultsch M]]
[[Category: Wells JA]]