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==Crystal structure of a human tyrosyl-tRNA synthetase mutant== | ==Crystal structure of a human tyrosyl-tRNA synthetase mutant== | ||
<StructureSection load='5thh' size='340' side='right' caption='[[5thh]], [[Resolution|resolution]] 1.96Å' scene=''> | <StructureSection load='5thh' size='340' side='right'caption='[[5thh]], [[Resolution|resolution]] 1.96Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5thh]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5THH OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5thh]] is a 1 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=5THH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5THH FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.959Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TYR:TYROSINE'>TYR</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=5thh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5thh OCA], [https://pdbe.org/5thh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5thh RCSB], [https://www.ebi.ac.uk/pdbsum/5thh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5thh ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/SYYC_HUMAN SYYC_HUMAN] Defects in YARS are the cause of Charcot-Marie-Tooth disease dominant intermediate type C (CMTDIC) [MIM:[https://omim.org/entry/608323 608323]. CMTDIC is a form of Charcot-Marie-Tooth disease characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.<ref>PMID:16429158</ref> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/SYYC_HUMAN SYYC_HUMAN] Catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr) (By similarity). | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
While having multiple aminoacyl-tRNA synthetases implicated in Charcot-Marie-Tooth (CMT) disease suggests a common mechanism, a defect in enzymatic activity is not shared among the CMT-causing mutants. Protein misfolding is a common hypothesis underlying the development of many neurological diseases. Its process usually involves an initial reduction in protein stability and then the subsequent oligomerization and aggregation. Here, we study the structural effect of three CMT-causing mutations in tyrosyl-tRNA synthetase (TyrRS or YARS). Through various approaches, we found that the mutations do not induce changes in protein secondary structures, or shared effects on oligomerization state and stability. However, all mutations provide access to a surface masked in the wild-type enzyme, and that access correlates with protein misinteraction. With recent data on another CMT-linked tRNA synthetase, we suggest that an inherent plasticity, engendering the formation of alternative stable conformations capable of aberrant interactions, links the tRNA synthetase family to CMT. | |||
Alternative stable conformation capable of protein misinteraction links tRNA synthetase to peripheral neuropathy.,Blocquel D, Li S, Wei N, Daub H, Sajish M, Erfurth ML, Kooi G, Zhou J, Bai G, Schimmel P, Jordanova A, Yang XL Nucleic Acids Res. 2017 May 22. doi: 10.1093/nar/gkx455. PMID:28531329<ref>PMID:28531329</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5thh" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Blocquel D]] | ||
[[Category: | [[Category: Yang XL]] | ||
Latest revision as of 16:01, 4 October 2023
Crystal structure of a human tyrosyl-tRNA synthetase mutantCrystal structure of a human tyrosyl-tRNA synthetase mutant
Structural highlights
DiseaseSYYC_HUMAN Defects in YARS are the cause of Charcot-Marie-Tooth disease dominant intermediate type C (CMTDIC) [MIM:608323. CMTDIC is a form of Charcot-Marie-Tooth disease characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.[1] FunctionSYYC_HUMAN Catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr) (By similarity). Publication Abstract from PubMedWhile having multiple aminoacyl-tRNA synthetases implicated in Charcot-Marie-Tooth (CMT) disease suggests a common mechanism, a defect in enzymatic activity is not shared among the CMT-causing mutants. Protein misfolding is a common hypothesis underlying the development of many neurological diseases. Its process usually involves an initial reduction in protein stability and then the subsequent oligomerization and aggregation. Here, we study the structural effect of three CMT-causing mutations in tyrosyl-tRNA synthetase (TyrRS or YARS). Through various approaches, we found that the mutations do not induce changes in protein secondary structures, or shared effects on oligomerization state and stability. However, all mutations provide access to a surface masked in the wild-type enzyme, and that access correlates with protein misinteraction. With recent data on another CMT-linked tRNA synthetase, we suggest that an inherent plasticity, engendering the formation of alternative stable conformations capable of aberrant interactions, links the tRNA synthetase family to CMT. Alternative stable conformation capable of protein misinteraction links tRNA synthetase to peripheral neuropathy.,Blocquel D, Li S, Wei N, Daub H, Sajish M, Erfurth ML, Kooi G, Zhou J, Bai G, Schimmel P, Jordanova A, Yang XL Nucleic Acids Res. 2017 May 22. doi: 10.1093/nar/gkx455. PMID:28531329[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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