4bb2: Difference between revisions
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The entry | ==Crystal structure of cleaved corticosteroid-binding globulin in complex with progesterone== | ||
<StructureSection load='4bb2' size='340' side='right'caption='[[4bb2]], [[Resolution|resolution]] 2.48Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4bb2]] 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=4BB2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BB2 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]] 2.48Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CYS:CYSTEINE'>CYS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=STR:PROGESTERONE'>STR</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=4bb2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bb2 OCA], [https://pdbe.org/4bb2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bb2 RCSB], [https://www.ebi.ac.uk/pdbsum/4bb2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bb2 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/CBG_HUMAN CBG_HUMAN] Corticosteroid-binding globulin deficiency. The disease is caused by mutations affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CBG_HUMAN CBG_HUMAN] Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.<ref>PMID:18513745</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Corticosteroid-binding globulin (CBG) transports glucocorticoids and progesterone in the blood and thereby modulates the tissue availability of these hormones. As a member of the serine protease inhibitor (SERPIN) family, CBG displays a reactive center loop (RCL) that is targeted by proteinases. Cleavage of the RCL is thought to trigger a SERPIN-typical stressed-to-relaxed (S-to-R) transition that leads to marked structural rearrangements and a reduced steroid-binding affinity. To characterize structure-function relationships in CBG we studied various conformational states of E. coli-produced rat and human CBG. In the 2.5 A crystal structure of human CBG in complex with progesterone, the RCL is cleaved at a novel site that differs from the known human neutrophil elastase recognition site. Although the cleaved RCL segment is five residues longer than anticipated, it becomes an integral part of beta-sheet A as a result of the S-to-R transition. The atomic interactions observed between progesterone and CBG explain the lower affinity of progesterone in comparison to corticosteroids. Surprisingly, CD measurements in combination with thermal unfolding experiments show that rat CBG fails to undergo an S-to-R transition upon proteolytic cleavage of the RCL hinting that the S-to-R transition observed in human CBG is not a prerequisite for CBG function in rat. This observation cautions against drawing general conclusions about molecular mechanisms by comparing and merging structural data from different species. | |||
Corticosteroid-binding globulin: structure-function implications from species differences.,Gardill BR, Vogl MR, Lin HY, Hammond GL, Muller YA PLoS One. 2012;7(12):e52759. doi: 10.1371/journal.pone.0052759. Epub 2012 Dec 26. PMID:23300763<ref>PMID:23300763</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4bb2" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Corticosteroid-binding globulin|Corticosteroid-binding globulin]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Gardill BR]] | |||
[[Category: Hammond GL]] | |||
[[Category: Lin H]] | |||
[[Category: Muller YA]] | |||
[[Category: Vogl MR]] | |||
Latest revision as of 14:47, 20 December 2023
Crystal structure of cleaved corticosteroid-binding globulin in complex with progesteroneCrystal structure of cleaved corticosteroid-binding globulin in complex with progesterone
Structural highlights
DiseaseCBG_HUMAN Corticosteroid-binding globulin deficiency. The disease is caused by mutations affecting the gene represented in this entry. FunctionCBG_HUMAN Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.[1] Publication Abstract from PubMedCorticosteroid-binding globulin (CBG) transports glucocorticoids and progesterone in the blood and thereby modulates the tissue availability of these hormones. As a member of the serine protease inhibitor (SERPIN) family, CBG displays a reactive center loop (RCL) that is targeted by proteinases. Cleavage of the RCL is thought to trigger a SERPIN-typical stressed-to-relaxed (S-to-R) transition that leads to marked structural rearrangements and a reduced steroid-binding affinity. To characterize structure-function relationships in CBG we studied various conformational states of E. coli-produced rat and human CBG. In the 2.5 A crystal structure of human CBG in complex with progesterone, the RCL is cleaved at a novel site that differs from the known human neutrophil elastase recognition site. Although the cleaved RCL segment is five residues longer than anticipated, it becomes an integral part of beta-sheet A as a result of the S-to-R transition. The atomic interactions observed between progesterone and CBG explain the lower affinity of progesterone in comparison to corticosteroids. Surprisingly, CD measurements in combination with thermal unfolding experiments show that rat CBG fails to undergo an S-to-R transition upon proteolytic cleavage of the RCL hinting that the S-to-R transition observed in human CBG is not a prerequisite for CBG function in rat. This observation cautions against drawing general conclusions about molecular mechanisms by comparing and merging structural data from different species. Corticosteroid-binding globulin: structure-function implications from species differences.,Gardill BR, Vogl MR, Lin HY, Hammond GL, Muller YA PLoS One. 2012;7(12):e52759. doi: 10.1371/journal.pone.0052759. Epub 2012 Dec 26. PMID:23300763[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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