7zli: Difference between revisions
New page: '''Unreleased structure''' The entry 7zli is ON HOLD Authors: Description: Category: Unreleased Structures |
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The | ==Cryo-EM structure of C-mannosyltransferase CeDPY19, in complex with Dol25-P-Man and bound to CMT2-Fab and anti-Fab nanobody== | ||
<StructureSection load='7zli' size='340' side='right'caption='[[7zli]], [[Resolution|resolution]] 2.99Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7zli]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ZLI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZLI FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.99Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IZY:[(2~{S},3~{S},4~{S},5~{S},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]+[(3~{S},6~{Z},10~{E},14~{E})-3,7,11,15,19-pentamethylicosa-6,10,14,18-tetraenyl]+hydrogen+phosphate'>IZY</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=7zli FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zli OCA], [https://pdbe.org/7zli PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zli RCSB], [https://www.ebi.ac.uk/pdbsum/7zli PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zli ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q7Z3Y4_HUMAN Q7Z3Y4_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
C-linked glycosylation is essential for the trafficking, folding and function of secretory and transmembrane proteins involved in cellular communication processes. The tryptophan C-mannosyltransferase (CMT) enzymes that install the modification attach a mannose to the first tryptophan of WxxW/C sequons in nascent polypeptide chains by an unknown mechanism. Here, we report cryogenic-electron microscopy structures of Caenorhabditis elegans CMT in four key states: apo, acceptor peptide-bound, donor-substrate analog-bound and as a trapped ternary complex with both peptide and a donor-substrate mimic bound. The structures indicate how the C-mannosylation sequon is recognized by this CMT and its paralogs, and how sequon binding triggers conformational activation of the donor substrate: a process relevant to all glycosyltransferase C superfamily enzymes. Our structural data further indicate that the CMTs adopt an unprecedented electrophilic aromatic substitution mechanism to enable the C-glycosylation of proteins. These results afford opportunities for understanding human disease and therapeutic targeting of specific CMT paralogs. | |||
Structure, sequon recognition and mechanism of tryptophan C-mannosyltransferase.,Bloch JS, John A, Mao R, Mukherjee S, Boilevin J, Irobalieva RN, Darbre T, Scott NE, Reymond JL, Kossiakoff AA, Goddard-Borger ED, Locher KP Nat Chem Biol. 2023 May;19(5):575-584. doi: 10.1038/s41589-022-01219-9. Epub 2023 , Jan 5. PMID:36604564<ref>PMID:36604564</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7zli" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Caenorhabditis elegans]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Bloch JS]] | |||
[[Category: Boilevin J]] | |||
[[Category: Darbre T]] | |||
[[Category: Goddard-Borger ED]] | |||
[[Category: Irobalieva R]] | |||
[[Category: Kossiakoff AA]] | |||
[[Category: Locher KP]] | |||
[[Category: Mukherjee S]] | |||
[[Category: Reymond JL]] | |||
Latest revision as of 17:17, 6 November 2024
Cryo-EM structure of C-mannosyltransferase CeDPY19, in complex with Dol25-P-Man and bound to CMT2-Fab and anti-Fab nanobodyCryo-EM structure of C-mannosyltransferase CeDPY19, in complex with Dol25-P-Man and bound to CMT2-Fab and anti-Fab nanobody
Structural highlights
FunctionPublication Abstract from PubMedC-linked glycosylation is essential for the trafficking, folding and function of secretory and transmembrane proteins involved in cellular communication processes. The tryptophan C-mannosyltransferase (CMT) enzymes that install the modification attach a mannose to the first tryptophan of WxxW/C sequons in nascent polypeptide chains by an unknown mechanism. Here, we report cryogenic-electron microscopy structures of Caenorhabditis elegans CMT in four key states: apo, acceptor peptide-bound, donor-substrate analog-bound and as a trapped ternary complex with both peptide and a donor-substrate mimic bound. The structures indicate how the C-mannosylation sequon is recognized by this CMT and its paralogs, and how sequon binding triggers conformational activation of the donor substrate: a process relevant to all glycosyltransferase C superfamily enzymes. Our structural data further indicate that the CMTs adopt an unprecedented electrophilic aromatic substitution mechanism to enable the C-glycosylation of proteins. These results afford opportunities for understanding human disease and therapeutic targeting of specific CMT paralogs. Structure, sequon recognition and mechanism of tryptophan C-mannosyltransferase.,Bloch JS, John A, Mao R, Mukherjee S, Boilevin J, Irobalieva RN, Darbre T, Scott NE, Reymond JL, Kossiakoff AA, Goddard-Borger ED, Locher KP Nat Chem Biol. 2023 May;19(5):575-584. doi: 10.1038/s41589-022-01219-9. Epub 2023 , Jan 5. PMID:36604564[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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