7ZLI
Cryo-EM structure of C-mannosyltransferase CeDPY19, in complex with Dol25-P-Man and bound to CMT2-Fab and anti-Fab nanobody
Summary for 7ZLI
| Entry DOI | 10.2210/pdb7zli/pdb |
| EMDB information | 14781 |
| Descriptor | CMT2-Fab heavy chain, Anti-Fab nanobody, CMT2-Fab light chain, ... (6 entities in total) |
| Functional Keywords | c-mannosyltransferase, membrane protein |
| Biological source | synthetic construct More |
| Total number of polymer chains | 4 |
| Total formula weight | 143125.46 |
| Authors | Bloch, J.S.,Mukherjee, S.,Boilevin, J.,Irobalieva, R.,Darbre, T.,Reymond, J.L.,Kossiakoff, A.A.,Goddard-Borger, E.D.,Locher, K.P. (deposition date: 2022-04-15, release date: 2023-01-11, Last modification date: 2024-11-06) |
| Primary citation | Bloch, J.S.,John, A.,Mao, R.,Mukherjee, S.,Boilevin, J.,Irobalieva, R.N.,Darbre, T.,Scott, N.E.,Reymond, J.L.,Kossiakoff, A.A.,Goddard-Borger, E.D.,Locher, K.P. Structure, sequon recognition and mechanism of tryptophan C-mannosyltransferase. Nat.Chem.Biol., 19:575-584, 2023 Cited by PubMed Abstract: 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. PubMed: 36604564DOI: 10.1038/s41589-022-01219-9 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.99 Å) |
Structure validation
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