6fwd

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Current revision (07:48, 7 February 2024) (edit) (undo)
 
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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6fwd]] 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=6FWD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FWD FirstGlance]. <br>
<table><tr><td colspan='2'>[[6fwd]] 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=6FWD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FWD FirstGlance]. <br>
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</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=6fwd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fwd OCA], [https://pdbe.org/6fwd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fwd RCSB], [https://www.ebi.ac.uk/pdbsum/6fwd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fwd ProSAT]</span></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]] 1.576&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6fwd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fwd OCA], [https://pdbe.org/6fwd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fwd RCSB], [https://www.ebi.ac.uk/pdbsum/6fwd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fwd ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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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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Hereditary transthyretin amyloidosis (ATTR) is an autosomal dominant disease characterized by the extracellular deposition of the transport protein transthyretin (TTR) as amyloid fibrils. Despite the progress achieved in recent years, understanding why different TTR residue substitutions lead to different clinical manifestations remains elusive. Here, we studied the molecular basis of disease-causing missense mutations affecting residues R34 and K35. R34G and K35T variants cause vitreous amyloidosis, whereas R34T and K35N mutations result in amyloid polyneuropathy and restrictive cardiomyopathy. All variants are more sensitive to pH-induced dissociation and amyloid formation than the wild-type (WT)-TTR counterpart, specifically in the variants deposited in the eyes amyloid formation occurs close to physiological pHs. Chemical denaturation experiments indicate that all the mutants are less stable than WT-TTR, with the vitreous amyloidosis variants, R34G and K35T, being highly destabilized. Sequence-induced stabilization of the dimer-dimer interface with T119M rendered tetramers containing R34G or K35T mutations resistant to pH-induced aggregation. Because R34 and K35 are among the residues more distant to the TTR interface, their impact in this region is therefore theorized to occur at long range. The crystal structures of double mutants, R34G/T119M and K35T/T119M, together with molecular dynamics simulations indicate that their strong destabilizing effect is initiated locally at the BC loop, increasing its flexibility in a mutation-dependent manner. Overall, the present findings help us to understand the sequence-dynamic-structural mechanistic details of TTR amyloid aggregation triggered by R34 and K35 variants and to link the degree of mutation-induced conformational flexibility to protein aggregation propensity.
 
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Disease-associated mutations impacting BC-loop flexibility trigger long-range transthyretin tetramer destabilization and aggregation.,Esperante SA, Varejao N, Pinheiro F, Sant'Anna R, Luque-Ortega JR, Alfonso C, Sora V, Papaleo E, Rivas G, Reverter D, Ventura S J Biol Chem. 2021 Sep;297(3):101039. doi: 10.1016/j.jbc.2021.101039. Epub 2021 , Jul 31. PMID:34343569<ref>PMID:34343569</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 6fwd" style="background-color:#fffaf0;"></div>
 
==See Also==
==See Also==

Current revision

Crystal structure of human transthyretin double mutant R34G/T119M at pH 5.5

PDB ID 6fwd

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

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