8ath
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==CRYSTAL STRUCTURE OF LAMP1 IN COMPLEX WITH FAB-B.== | |
| + | <StructureSection load='8ath' size='340' side='right'caption='[[8ath]], [[Resolution|resolution]] 2.37Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8ath]] 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=8ATH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ATH FirstGlance]. <br> | ||
| + | </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=8ath FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ath OCA], [https://pdbe.org/8ath PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ath RCSB], [https://www.ebi.ac.uk/pdbsum/8ath PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ath ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/LAMP1_HUMAN LAMP1_HUMAN] Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, autophagy, and cholesterol homeostasis (By similarity). Also plays an important role in NK-cells cytotoxicity (PubMed:23632890, PubMed:2022921). Mechanistically, participates in cytotoxic granule movement to the cell surface and perforin trafficking to the lytic granule (PubMed:23632890). In addition, protects NK-cells from degranulation-associated damage induced by their own cytotoxic granule content (PubMed:23847195). Presents carbohydrate ligands to selectins. Also implicated in tumor cell metastasis.[UniProtKB:P11438]<ref>PMID:2022921</ref> <ref>PMID:23632890</ref> <ref>PMID:23847195</ref> (Microbial infection) Acts as a receptor for Lassa virus glycoprotein (PubMed:24970085, PubMed:25972533, PubMed:27605678, PubMed:28448640). Promotes also fusion of the virus with host membrane in less acidic endosomes (PubMed:29295909).<ref>PMID:24970085</ref> <ref>PMID:25972533</ref> <ref>PMID:27605678</ref> <ref>PMID:28448640</ref> <ref>PMID:29295909</ref> (Microbial infection) Supports the FURIN-mediated cleavage of mumps virus fusion protein F by interacting with both FURIN and the unprocessed form but not the processed form of the viral protein F.<ref>PMID:32295904</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Delineating the precise regions on an antigen that are targeted by antibodies has become a key step for the development of antibody therapeutics. X-ray crystallography and cryogenic electron microscopy are considered the gold standard for providing precise information about these binding sites at atomic resolution. However, they are labor-intensive and a successful outcome is not guaranteed. We used deep mutational scanning (DMS) of the human LAMP-1 antigen displayed on yeast surface and leveraged next-generation sequencing to observe the effect of individual mutants on the binding of two LAMP-1 antibodies and to determine their functional epitopes on LAMP-1. Fine-tuned epitope mapping by DMS approaches is augmented by knowledge of experimental antigen structure. As human LAMP-1 structure has not yet been solved, we used the AlphaFold predicted structure of the full-length protein to combine with DMS data and ultimately finely map antibody epitopes. The accuracy of this method was confirmed by comparing the results to the co-crystal structure of one of the two antibodies with a LAMP-1 luminal domain. Finally, we used AlphaFold models of non-human LAMP-1 to understand the lack of mAb cross-reactivity. While both epitopes in the murine form exhibit multiple mutations in comparison to human LAMP-1, only one and two mutations in the Macaca form suffice to hinder the recognition by mAb B and A, respectively. Altogether, this study promotes a new application of AlphaFold to speed up precision mapping of antibody-antigen interactions and consequently accelerate antibody engineering for optimization. | ||
| - | + | Deciphering cross-species reactivity of LAMP-1 antibodies using deep mutational epitope mapping and AlphaFold.,Pruvost T, Mathieu M, Dubois S, Maillere B, Vigne E, Nozach H MAbs. 2023 Jan-Dec;15(1):2175311. doi: 10.1080/19420862.2023.2175311. PMID:36797224<ref>PMID:36797224</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8ath" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Dupuy A]] | ||
| + | [[Category: Mathieu M]] | ||
Revision as of 06:01, 2 March 2023
CRYSTAL STRUCTURE OF LAMP1 IN COMPLEX WITH FAB-B.
| |||||||||||
