4mrb

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Current revision (12:28, 1 March 2024) (edit) (undo)
 
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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4mrb]] 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=4MRB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MRB FirstGlance]. <br>
<table><tr><td colspan='2'>[[4mrb]] 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=4MRB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MRB FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.27&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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=4mrb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mrb OCA], [https://pdbe.org/4mrb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mrb RCSB], [https://www.ebi.ac.uk/pdbsum/4mrb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mrb ProSAT]</span></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=4mrb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mrb OCA], [https://pdbe.org/4mrb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mrb RCSB], [https://www.ebi.ac.uk/pdbsum/4mrb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mrb ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/TTHY_HUMAN TTHY_HUMAN] Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.<ref>PMID:3714052</ref>
[https://www.uniprot.org/uniprot/TTHY_HUMAN TTHY_HUMAN] Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.<ref>PMID:3714052</ref>
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<div style="background-color:#fffaf0;">
 
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== Publication Abstract from PubMed ==
 
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The Ser52Pro variant of transthyretin (TTR) produces aggressive, highly penetrant, autosomal-dominant systemic amyloidosis in persons heterozygous for the causative mutation. Together with a minor quantity of full-length wild-type and variant TTR, the main component of the ex vivo fibrils was the residue 49-127 fragment of the TTR variant, the portion of the TTR sequence that previously has been reported to be the principal constituent of type A, cardiac amyloid fibrils formed from wild-type TTR and other TTR variants [Bergstrom J, et al. (2005) J Pathol 206(2):224-232]. This specific truncation of Ser52Pro TTR was generated readily in vitro by limited proteolysis. In physiological conditions and under agitation the residue 49-127 proteolytic fragment rapidly and completely self-aggregates into typical amyloid fibrils. The remarkable susceptibility to such cleavage is likely caused by localized destabilization of the beta-turn linking strands C and D caused by loss of the wild-type hydrogen-bonding network between the side chains of residues Ser52, Glu54, Ser50, and a water molecule, as revealed by the high-resolution crystallographic structure of Ser52Pro TTR. We thus provide a structural basis for the recently hypothesized, crucial pathogenic role of proteolytic cleavage in TTR amyloid fibrillogenesis. Binding of the natural ligands thyroxine or retinol-binding protein (RBP) by Ser52Pro variant TTR stabilizes the native tetrameric assembly, but neither protected the variant from proteolysis. However, binding of RBP, but not thyroxine, inhibited subsequent fibrillogenesis.
 
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Proteolytic cleavage of Ser52Pro variant transthyretin triggers its amyloid fibrillogenesis.,Mangione PP, Porcari R, Gillmore JD, Pucci P, Monti M, Porcari M, Giorgetti S, Marchese L, Raimondi S, Serpell LC, Chen W, Relini A, Marcoux J, Clatworthy IR, Taylor GW, Tennent GA, Robinson CV, Hawkins PN, Stoppini M, Wood SP, Pepys MB, Bellotti V Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1539-44. doi:, 10.1073/pnas.1317488111. Epub 2014 Jan 13. PMID:24474780<ref>PMID:24474780</ref>
 
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
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</div>
 
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<div class="pdbe-citations 4mrb" style="background-color:#fffaf0;"></div>
 
==See Also==
==See Also==

Current revision

Wild Type Human Transthyretin pH 7.5

PDB ID 4mrb

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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