3mzt

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{{STRUCTURE_3mzt| PDB=3mzt | SCENE= }}
 
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===Protein-induced photophysical changes to the amyloid indicator dye, thioflavin T===
 
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{{ABSTRACT_PUBMED_20826442}}
 
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==Disease==
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==Protein-induced photophysical changes to the amyloid indicator dye, thioflavin T==
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[[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref><ref>PMID:1336137</ref><ref>PMID:7554280</ref><ref>PMID:4586824</ref><ref>PMID:8084451</ref><ref>PMID:12119416</ref><ref>PMID:12796775</ref><ref>PMID:16901902</ref><ref>PMID:16491088</ref><ref>PMID:17646174</ref><ref>PMID:18835253</ref><ref>PMID:18395224</ref><ref>PMID:19284997</ref>
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<StructureSection load='3mzt' size='340' side='right'caption='[[3mzt]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3mzt]] is a 6 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=3MZT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MZT 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]] 2.7&#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=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=TFX:2-[4-(DIMETHYLAMINO)PHENYL]-3,6-DIMETHYL-1,3-BENZOTHIAZOL-3-IUM'>TFX</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=3mzt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mzt OCA], [https://pdbe.org/3mzt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mzt RCSB], [https://www.ebi.ac.uk/pdbsum/3mzt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mzt ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[https://omim.org/entry/241600 241600]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
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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/mz/3mzt_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3mzt 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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The small molecule thioflavin T (ThT) is a defining probe for the identification and mechanistic study of amyloid fiber formation. As such, ThT is fundamental to investigations of serious diseases such as Alzheimer's disease, Parkinson disease, and type II diabetes. For each disease, a different protein undergoes conformational conversion to a beta-sheet rich fiber. The fluorescence of ThT exhibits an increase in quantum yield upon binding these fibers. Despite its widespread use, the structural basis for binding specificity and for the changes to the photophysical properties of ThT remain poorly understood. Here, we report the co-crystal structures of ThT with two alternative states of beta-2 microglobulin (beta2m); one monomeric, the other an amyloid-like oligomer. In the latter, the dye intercalates between beta-sheets orthogonal to the beta-strands. Importantly, the fluorophore is bound in such a manner that a photophysically relevant torsion is limited to a range of angles generally associated with low, not high, quantum yield. Quantum mechanical assessment of the fluorophore shows the electronic distribution to be strongly stabilized by aromatic interactions with the protein. Monomeric beta2m gives little increase in ThT fluorescence despite showing three fluorophores, at two binding sites, in configurations generally associated with high quantum yield. Our efforts fundamentally extend existing understanding about the origins of amyloid-induced photophysical changes. Specifically, the beta-sheet interface that characterizes amyloid acts both sterically and electronically to stabilize the fluorophore's ground state electronic distribution. By preventing the fluorophore from adopting its preferred excited state configuration, nonradiative relaxation pathways are minimized and quantum yield is increased.
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==Function==
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Protein-induced photophysical changes to the amyloid indicator dye thioflavin T.,Wolfe LS, Calabrese MF, Nath A, Blaho DV, Miranker AD, Xiong Y Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16863-8. Epub 2010 Sep 8. PMID:20826442<ref>PMID:20826442</ref>
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[[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3mzt]] is a 6 chain structure with 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=3MZT OCA].
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</div>
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<div class="pdbe-citations 3mzt" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[Beta-2 microglobulin|Beta-2 microglobulin]]
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*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:020826442</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Blaho, D V.]]
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[[Category: Large Structures]]
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[[Category: Calabrese, M F.]]
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[[Category: Blaho DV]]
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[[Category: Miranker, A D.]]
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[[Category: Calabrese MF]]
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[[Category: Nath, A.]]
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[[Category: Miranker AD]]
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[[Category: Wolfe, L S.]]
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[[Category: Nath A]]
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[[Category: Xiong, Y.]]
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[[Category: Wolfe LS]]
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[[Category: Alzheimers']]
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[[Category: Xiong Y]]
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[[Category: Amyloid]]
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[[Category: Immune system]]
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[[Category: Parkinsons']]
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[[Category: Thioflavin t]]
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Current revision

Protein-induced photophysical changes to the amyloid indicator dye, thioflavin T

PDB ID 3mzt

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