6BE2

Crystal structure of a polysaccharide-binding human Fab (F598)

6BE2 の概要

• エントリーDOI: 10.2210/pdb6be2/pdb
• 関連するPDBエントリー: 6BE3 6BE4
• 分子名称: Fab (F598) Heavy Chain, Fab (F598) Light Chain (3 entities in total)
• 機能のキーワード: immunoglobulin, human antibody, antigen binding fragment, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47297.52

構造登録者

Soliman, C.,Ramsland, P.A. (登録日: 2017-10-24, 公開日: 2018-02-21, 最終更新日: 2024-10-16)

主引用文献

Soliman, C.,Walduck, A.K.,Yuriev, E.,Richards, J.S.,Cywes-Bentley, C.,Pier, G.B.,Ramsland, P.A.
Structural basis for antibody targeting of the broadly expressed microbial polysaccharide poly-N-acetylglucosamine.
J. Biol. Chem., 293:5079-5089, 2018

PubMed Abstract: In response to the widespread emergence of antibiotic-resistant microbes, new therapeutic agents are required for many human pathogens. A non-mammalian polysaccharide, poly--acetyl-d-glucosamine (PNAG), is produced by bacteria, fungi, and protozoan parasites. Antibodies that bind to PNAG and its deacetylated form (dPNAG) exhibit promising and activities against many microbes. A human IgG1 mAb (F598) that binds both PNAG and dPNAG has opsonic and protective activities against multiple microbial pathogens and is undergoing preclinical and clinical assessments as a broad-spectrum antimicrobial therapy. Here, to understand how F598 targets PNAG, we determined crystal structures of the unliganded F598 antigen-binding fragment (Fab) and its complexes with -acetyl-d-glucosamine (GlcNAc) and a PNAG oligosaccharide. We found that F598 recognizes PNAG through a large groove-shaped binding site that traverses the entire light- and heavy-chain interface and accommodates at least five GlcNAc residues. The Fab-GlcNAc complex revealed a deep binding pocket in which the monosaccharide and a core GlcNAc of the oligosaccharide were almost identically positioned, suggesting an anchored binding mechanism of PNAG by F598. The Fab used in our structural analyses retained binding to PNAG on the surface of an antibiotic-resistant, biofilm-forming strain of Additionally, a model of intact F598 binding to two pentasaccharide epitopes indicates that the Fab arms can span at least 40 GlcNAc residues on an extended PNAG chain. Our findings unravel the structural basis for F598 binding to PNAG on microbial surfaces and biofilms.

PubMed: 29449370
DOI: 10.1074/jbc.RA117.001170

実験手法

X-RAY DIFFRACTION (1.7 Å)