2k6t: Difference between revisions
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< | ==Solution structure of the relaxin-like factor== | ||
<StructureSection load='2k6t' size='340' side='right'caption='[[2k6t]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2k6t]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K6T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K6T FirstGlance]. <br> | |||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2h8b|2h8b]], [[2k6u|2k6u]]</div></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=2k6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k6t OCA], [https://pdbe.org/2k6t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k6t RCSB], [https://www.ebi.ac.uk/pdbsum/2k6t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k6t ProSAT]</span></td></tr> | ||
</table> | |||
== 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 == | |||
[[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. | |||
== 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/k6/2k6t_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2k6t ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Analogous 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<ref>PMID:19086273</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2k6t" style="background-color:#fffaf0;"></div> | |||
== References == | |||
--> | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
[[Category: Bullesbach, E E]] | |||
[[Category: Hansen, D F]] | |||
[[Category: Hass, M A.S]] | |||
[[Category: Jensen, M R]] | |||
[[Category: Bullesbach, E E | [[Category: Kristensen, S M]] | ||
[[Category: Hansen, D F | [[Category: Led, J J]] | ||
[[Category: Hass, M A.S | [[Category: Schwabe, C]] | ||
[[Category: Jensen, M R | |||
[[Category: Kristensen, S M | |||
[[Category: Led, J J | |||
[[Category: Schwabe, C | |||
[[Category: Cleavage on pair of basic residue]] | [[Category: Cleavage on pair of basic residue]] | ||
[[Category: Disease mutation]] | [[Category: Disease mutation]] | ||
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[[Category: Protein]] | [[Category: Protein]] | ||
[[Category: Secreted]] | [[Category: Secreted]] | ||
Latest revision as of 10:32, 27 January 2022
Solution structure of the relaxin-like factorSolution structure of the relaxin-like factor
Structural highlights
Disease[INSL3_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] Function[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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. 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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