2k6u: Difference between revisions
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==The Solution Structure of a Conformationally Restricted Fully Active Derivative of the Human Relaxin-like Factor (RLF)== | ==The Solution Structure of a Conformationally Restricted Fully Active Derivative of the Human Relaxin-like Factor (RLF)== | ||
<StructureSection load='2k6u' size='340' side='right' caption='[[2k6u | <StructureSection load='2k6u' size='340' side='right'caption='[[2k6u]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2k6u]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K6U OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[2k6u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K6U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K6U FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2k6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k6u OCA], [https://pdbe.org/2k6u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k6u RCSB], [https://www.ebi.ac.uk/pdbsum/2k6u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k6u ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/INSL3_HUMAN INSL3_HUMAN] Defects in INSL3 seems to be a cause of cryptorchidism (CRYPTO) [MIM:[https://omim.org/entry/219050 219050]; also known as impaired testicular descent. It is one of the most frequent congenital abnormalities in humans, involving 2-5% of male births. Cryptorchidism is associated with increased risk of infertility and testicular cancer. The frequency of INSL3 gene mutations as a cause of cryptorchidism is low.<ref>PMID:11095425</ref> <ref>PMID:11746019</ref> <ref>PMID:12601553</ref> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/INSL3_HUMAN INSL3_HUMAN] Seems to play a role in testicular function. May be a trophic hormone with a role in testicular descent in fetal life. Is a ligand for LGR8 receptor. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Bullesbach EE]] | ||
[[Category: | [[Category: Hansen DF]] | ||
[[Category: | [[Category: Hass MAS]] | ||
[[Category: | [[Category: Jensen MR]] | ||
[[Category: | [[Category: Kristensen SM]] | ||
[[Category: | [[Category: Led JJ]] | ||
[[Category: | [[Category: Schwabe C]] | ||
Latest revision as of 04:07, 21 November 2024
The Solution Structure of a Conformationally Restricted Fully Active Derivative of the Human Relaxin-like Factor (RLF)The Solution Structure of a Conformationally Restricted Fully Active Derivative of the Human Relaxin-like Factor (RLF)
Structural highlights
DiseaseINSL3_HUMAN Defects in INSL3 seems to be a cause of cryptorchidism (CRYPTO) [MIM:219050; also known as impaired testicular descent. It is one of the most frequent congenital abnormalities in humans, involving 2-5% of male births. Cryptorchidism is associated with increased risk of infertility and testicular cancer. The frequency of INSL3 gene mutations as a cause of cryptorchidism is low.[1] [2] [3] FunctionINSL3_HUMAN Seems to play a role in testicular function. May be a trophic hormone with a role in testicular descent in fetal life. Is a ligand for LGR8 receptor. Publication Abstract from PubMedAnalogous to insulin, the relaxin-like factor (RLF) must undergo a structural transition to the active form prior to receptor binding. Thus, the C-terminus of the B chain of RLF folds toward the surface of the central B chain helix, causing partial obliteration of the two essential RLF receptor-binding site residues, valine B19 and tryptophan B27. Via comparison of the solution structure of a fully active C-terminally cross-linked RLF analogue with the native synthetic human RLF (hRLF), it became clear that the cross-linked analogue largely retains the essential folding of the native protein. Both proteins exist in a major and minor conformation, as revealed by multiple resonances from tryptophan B27 and adjacent residues on the B chain helix. Notably, the minor conformation is significantly more highly populated in the chemically cross-linked RLF than it is in the hRLF. In addition, compared to the unmodified molecule, subtle differences are observed within the B chain helix whereby the cross-linked derivative shows a reduced level of hydrogen bonding and significant peak broadening at the binding site residue ValB19. On the basis of these observations, we suggest that the solution structure of the native hormone represents an inactive conformer and that a dynamic equilibrium exists between the C-terminally unfolded binding conformation and the inactive conformation of the RLF. Solution structure of a conformationally restricted fully active derivative of the human relaxin-like factor.,Bullesbach EE, Hass MA, Jensen MR, Hansen DF, Kristensen SM, Schwabe C, Led JJ Biochemistry. 2008 Dec 16;47(50):13308-17. PMID:19086273[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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