6mbk: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='6mbk' size='340' side='right'caption='[[6mbk]], [[Resolution|resolution]] 1.69Å' scene=''> | <StructureSection load='6mbk' size='340' side='right'caption='[[6mbk]], [[Resolution|resolution]] 1.69Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6mbk]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6mbk]] is a 4 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=6MBK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MBK FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.69Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6mbk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mbk OCA], [https://pdbe.org/6mbk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mbk RCSB], [https://www.ebi.ac.uk/pdbsum/6mbk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mbk 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/ACTB_HUMAN ACTB_HUMAN] Defects in ACTB are a cause of dystonia juvenile-onset (DYTJ) [MIM:[https://omim.org/entry/607371 607371]. DYTJ is a form of dystonia with juvenile onset. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYTJ patients manifest progressive, generalized, dopa-unresponsive dystonia, developmental malformations and sensory hearing loss.<ref>PMID:16685646</ref> Defects in ACTB are the cause of Baraitser-Winter syndrome type 1 (BRWS1) [MIM:[https://omim.org/entry/243310 243310]. A rare developmental disorder characterized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss.<ref>PMID:22366783</ref> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/ACTB_HUMAN ACTB_HUMAN] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 29: | Line 28: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Cheng | [[Category: Cheng X]] | ||
[[Category: Dai | [[Category: Dai S]] | ||
[[Category: Horton | [[Category: Horton JR]] | ||
Latest revision as of 09:28, 11 October 2023
SETD3, a Histidine Methyltransferase, in Complex with an Actin Peptide and SAH, First P212121 Crystal FormSETD3, a Histidine Methyltransferase, in Complex with an Actin Peptide and SAH, First P212121 Crystal Form
Structural highlights
DiseaseACTB_HUMAN Defects in ACTB are a cause of dystonia juvenile-onset (DYTJ) [MIM:607371. DYTJ is a form of dystonia with juvenile onset. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYTJ patients manifest progressive, generalized, dopa-unresponsive dystonia, developmental malformations and sensory hearing loss.[1] Defects in ACTB are the cause of Baraitser-Winter syndrome type 1 (BRWS1) [MIM:243310. A rare developmental disorder characterized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss.[2] FunctionACTB_HUMAN Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. Publication Abstract from PubMedFor more than 50 years, the methylation of mammalian actin at histidine 73 has been known to occur(1). Despite the pervasiveness of His73 methylation, which we find is conserved in several model animals and plants, its function remains unclear and the enzyme that generates this modification is unknown. Here we identify SET domain protein 3 (SETD3) as the physiological actin His73 methyltransferase. Structural studies reveal that an extensive network of interactions clamps the actin peptide onto the surface of SETD3 to orient His73 correctly within the catalytic pocket and to facilitate methyl transfer. His73 methylation reduces the nucleotide-exchange rate on actin monomers and modestly accelerates the assembly of actin filaments. Mice that lack SETD3 show complete loss of actin His73 methylation in several tissues, and quantitative proteomics analysis shows that actin His73 methylation is the only detectable physiological substrate of SETD3. SETD3-deficient female mice have severely decreased litter sizes owing to primary maternal dystocia that is refractory to ecbolic induction agents. Furthermore, depletion of SETD3 impairs signal-induced contraction in primary human uterine smooth muscle cells. Together, our results identify a mammalian histidine methyltransferase and uncover a pivotal role for SETD3 and actin His73 methylation in the regulation of smooth muscle contractility. Our data also support the broader hypothesis that protein histidine methylation acts as a common regulatory mechanism. SETD3 is an actin histidine methyltransferase that prevents primary dystocia.,Wilkinson AW, Diep J, Dai S, Liu S, Ooi YS, Song D, Li TM, Horton JR, Zhang X, Liu C, Trivedi DV, Ruppel KM, Vilches-Moure JG, Casey KM, Mak J, Cowan T, Elias JE, Nagamine CM, Spudich JA, Cheng X, Carette JE, Gozani O Nature. 2019 Jan;565(7739):372-376. doi: 10.1038/s41586-018-0821-8. Epub 2018 Dec, 10. PMID:30626964[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||