3d7p

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{{Seed}}
 
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[[Image:3d7p.jpg|left|200px]]
 
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==Crystal structure of human Transthyretin (TTR) at pH 4.0==
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The line below this paragraph, containing "STRUCTURE_3d7p", creates the "Structure Box" on the page.
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<StructureSection load='3d7p' size='340' side='right'caption='[[3d7p]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3d7p]] 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=3D7P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D7P FirstGlance]. <br>
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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]] 1.72&#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=3d7p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d7p OCA], [https://pdbe.org/3d7p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d7p RCSB], [https://www.ebi.ac.uk/pdbsum/3d7p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d7p ProSAT]</span></td></tr>
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{{STRUCTURE_3d7p| PDB=3d7p | SCENE= }}
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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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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d7/3d7p_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=3d7p ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Acidification of the transthyretin (TTR) tetramer facilitates dissociation and conformational changes in the protein, allowing alternatively folded monomers to self-assemble into insoluble amyloid fibers by a downhill polymerization mechanism in vitro. To investigate the influence of acidification on the quaternary and tertiary structures of TTR, crystal structures of wild-type human TTR at pH 4.0 and pH 3.5 have been determined to 1.7 A resolution. The acidic pH crystals are isomorphous to most of the previously reported TTR structures, containing two subunits in the asymmetric unit (the so-called A and B subunits) but forming a tetramer through crystallographic symmetry. The pH 4.0 crystal structure reveals that the native fold of the tetramer remains mostly undisturbed. In particular, subunit A of the TTR pH 4.0 structure is very similar to the wild-type TTR pH 7.4 structure with an r.m.s.d. of 0.38 A. In contrast, subunit B of the TTR pH 4.0 structure exhibits several significant changes. The EF-helix (residues 75-81) and the adjacent EF-loop (residues 82-90) show an r.m.s.d. greater than 2.0 A. The acidic residues within this region (Glu72, Asp74, Glu89, and Glu92) undergo significant conformational changes that instigate movement of the EF helix-loop region and make residues Lys70, Lys76, His88, and His90 orient their side chains toward these acidic residues. In particular, Glu89 undergoes a maximum deviation of 5.6 A, occupying Phe87's initial position in the wild-type TTR pH 7.4 structure, and points its side chain into a hydrophobic pocket of the neighboring subunit. In the pH 3.5 structure, the EF helix-loop region is completely disordered. These results demonstrate that acidic conditions increase the susceptibility of the EF helix-loop region of the TTR B subunit to undergo conformational changes and unfold, likely destabilizing the tetramer and identifying at least the initial conformational changes likely occurring within the tetramer that leads to the amyloidogenic monomer.
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===Crystal structure of human Transthyretin (TTR) at pH 4.0===
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Structural insight into pH-induced conformational changes within the native human transthyretin tetramer.,Palaninathan SK, Mohamedmohaideen NN, Snee WC, Kelly JW, Sacchettini JC J Mol Biol. 2008 Oct 24;382(5):1157-67. Epub 2008 Jul 16. PMID:18662699<ref>PMID:18662699</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 3d7p" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_18662699}}, adds the Publication Abstract to the page
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*[[Transthyretin 3D structures|Transthyretin 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 18662699 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_18662699}}
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__TOC__
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</StructureSection>
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==About this Structure==
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3D7P is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D7P OCA].
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==Reference==
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Structural Insight into pH-Induced Conformational Changes within the Native Human Transthyretin Tetramer., Palaninathan SK, Mohamed Mohaideen NN, Snee WC, Kelly JW, Sacchettini JC, J Mol Biol. 2008 Jul 16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18662699 18662699]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Kelly,J W.]]
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[[Category: Kelly JW]]
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[[Category: Mohamedmohaideen,N N.]]
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[[Category: Mohamedmohaideen NN]]
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[[Category: Palaninathan,S K.]]
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[[Category: Palaninathan SK]]
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[[Category: Sacchettini,J C.]]
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[[Category: Sacchettini JC]]
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[[Category: Snee,W C.]]
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[[Category: Snee WC]]
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[[Category: Acidic ph]]
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[[Category: Amyloid]]
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[[Category: And crystal structure]]
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[[Category: Disease mutation]]
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[[Category: Gamma-carboxyglutamic acid]]
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[[Category: Glycoprotein]]
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[[Category: Hormone]]
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[[Category: Native ttr]]
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[[Category: Polymorphism]]
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[[Category: Polyneuropathy]]
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[[Category: Retinol-binding]]
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[[Category: Secreted]]
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[[Category: Thyroid hormone]]
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[[Category: Transport]]
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[[Category: Transport protein]]
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[[Category: Transthyretin]]
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[[Category: Vitamin some]]
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[[Category: Wt-ttr]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Aug 13 14:06:21 2008''
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Current revision

Crystal structure of human Transthyretin (TTR) at pH 4.0

PDB ID 3d7p

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