7wl6

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'''Unreleased structure'''
 
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The entry 7wl6 is ON HOLD until Paper Publication
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==Crystal structure of I73L mutated human transthyretin==
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<StructureSection load='7wl6' size='340' side='right'caption='[[7wl6]], [[Resolution|resolution]] 1.42&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[7wl6]] 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=7WL6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WL6 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=MG:MAGNESIUM+ION'>MG</scene></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=7wl6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wl6 OCA], [https://pdbe.org/7wl6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wl6 RCSB], [https://www.ebi.ac.uk/pdbsum/7wl6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wl6 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/TTHY_HUMAN TTHY_HUMAN] Defects in TTR are the cause of amyloidosis transthyretin-related (AMYL-TTR) [MIM:[https://omim.org/entry/105210 105210]. A hereditary generalized amyloidosis due to transthyretin amyloid deposition. Protein fibrils can form in different tissues leading to amyloid polyneuropathies, amyloidotic cardiomyopathy, carpal tunnel syndrome, systemic senile amyloidosis. The disease includes leptomeningeal amyloidosis that is characterized by primary involvement of the central nervous system. Neuropathologic examination shows amyloid in the walls of leptomeningeal vessels, in pia arachnoid, and subpial deposits. Some patients also develop vitreous amyloid deposition that leads to visual impairment (oculoleptomeningeal amyloidosis). Clinical features include seizures, stroke-like episodes, dementia, psychomotor deterioration, variable amyloid deposition in the vitreous humor.<ref>PMID:11243784</ref> <ref>PMID:15735344</ref> <ref>PMID:19167329</ref> <ref>PMID:3818577</ref> <ref>PMID:3022108</ref> <ref>PMID:6651852</ref> <ref>PMID:6583672</ref> <ref>PMID:3135807</ref> <ref>PMID:1517749</ref> <ref>PMID:1932142</ref> <ref>PMID:7923855</ref> <ref>PMID:8382610</ref> <ref>PMID:8428915</ref> <ref>PMID:9733771</ref> <ref>PMID:12403615</ref> <ref>PMID:16185074</ref> <ref>PMID:16627944</ref> <ref>PMID:6487335</ref> <ref>PMID:3722385</ref> <ref>PMID:2891727</ref> <ref>PMID:2161654</ref> <ref>PMID:2363717</ref> <ref>PMID:1656975</ref> <ref>PMID:2046936</ref> <ref>PMID:1570831</ref> <ref>PMID:1734866</ref> <ref>PMID:1520326</ref> <ref>PMID:1520336</ref> <ref>PMID:1544214</ref> <ref>PMID:1351039</ref> <ref>PMID:1301926</ref> <ref>PMID:1362222</ref> <ref>PMID:1436517</ref> <ref>PMID:8352764</ref> <ref>PMID:8038017</ref> <ref>PMID:8257997</ref> <ref>PMID:8095302</ref> <ref>PMID:1997217</ref> <ref>PMID:8019560</ref> <ref>PMID:8081397</ref> <ref>PMID:7914929</ref> <ref>PMID:8133316</ref> <ref>PMID:7910950</ref> <ref>PMID:7655883</ref> <ref>PMID:7850982</ref> <ref>PMID:8579098</ref> <ref>PMID:9066351</ref> <ref>PMID:8990019</ref> <ref>PMID:9605286</ref> <ref>PMID:10036587</ref> <ref>PMID:10627135</ref> <ref>PMID:10694917</ref> <ref>PMID:10211412</ref> <ref>PMID:10439117</ref> <ref>PMID:10611950</ref> <ref>PMID:10071047</ref> <ref>PMID:10436378</ref> <ref>PMID:10842705</ref> <ref>PMID:10842718</ref> <ref>PMID:10882995</ref> <ref>PMID:11445644</ref> <ref>PMID:12557757</ref> <ref>PMID:11866053</ref> <ref>PMID:12050338</ref> <ref>PMID:12771253</ref> <ref>PMID:15214015</ref> <ref>PMID:15478468</ref> <ref>PMID:15217993</ref> <ref>PMID:17453626</ref> <ref>PMID:17577687</ref> <ref>PMID:17503405</ref> <ref>PMID:17635579</ref> Defects in TTR are a cause of hyperthyroxinemia dystransthyretinemic euthyroidal (HTDE) [MIM:[https://omim.org/entry/145680 145680]. It is a condition characterized by elevation of total and free thyroxine in healthy, euthyroid persons without detectable binding protein abnormalities.<ref>PMID:1979335</ref> Defects in TTR are a cause of carpal tunnel syndrome type 1 (CTS1) [MIM:[https://omim.org/entry/115430 115430]. It is a condition characterized by entrapment of the median nerve within the carpal tunnel. Symptoms include burning pain and paresthesias involving the ventral surface of the hand and fingers which may radiate proximally. Impairment of sensation in the distribution of the median nerve and thenar muscle atrophy may occur. This condition may be associated with repetitive occupational trauma, wrist injuries, amyloid neuropathies, rheumatoid arthritis.<ref>PMID:8309582</ref>
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== Function ==
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[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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Destabilization of human transthyretin leads to its aggregation into amyloid fibrils, which causes a rare, progressive and fatal systemic disorder called ATTR amyloidosis. By contrast, murine transthyretin is known to be very stable and therefore does not aggregate into amyloid fibrils in vivo or in vitro. We examined the hydrophobic residues responsible for the high-stability and low-aggregation properties of murine transthyretin using site-directed mutagenesis. Urea-induced unfolding and thioflavin T fluorescence aggregation assay revealed that Leu73 of murine transthyretin largely contributes to its high stability and low aggregation properties: the I73L mutation stabilized human transthyretin, while the L73I mutation destabilized murine transthyretin. In addition, the I26V/I73L mutation stabilized the amyloidogenic V30M mutant of human transthyretin to the same degree as the suppressor mutation T119M, which protects transthyretin against amyloid fibril aggregation. The I73L mutation resulted in no significant differences in the overall structure of the transthyretin tetramer or the contacts of side-chains in the hydrophobic core of the monomer. We also found that Leu73 of murine transthyretin is conserved in many mammals, while Ile73 of human transthyretin is conserved in monkeys and cats. These studies will provide new insights into the stability and aggregation properties of transthyretin from various mammals.
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Authors:
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The hydrophobic residue Leu73 is crucial for the high stability and low aggregation properties of murine transthyretin.,Nakagawa M, Obita T, Mizuguchi M Biochem J. 2022 Sep 30;479(18):1999-2011. doi: 10.1042/BCJ20220203. PMID:36098398<ref>PMID:36098398</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 7wl6" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Mizuguchi M]]
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[[Category: Nakagawa M]]
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[[Category: Obita T]]

Revision as of 10:08, 24 November 2022

Crystal structure of I73L mutated human transthyretin

PDB ID 7wl6

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