7UEN

Genetic and structural basis of the human anti-alpha-galactosyl antibody response

「6NUY」から置き換えられました

7UEN の概要

• エントリーDOI: 10.2210/pdb7uen/pdb
• 分子名称: M86 antibody Fab light chain, M86 antibody Fab heavy chain, alpha-D-galactopyranose-(1-3)-beta-D-galactopyranose, ... (6 entities in total)
• 機能のキーワード: alpha-galactosyl, antibody, anti-alpha-gal, immune response, m86, immune system
• 由来する生物種: Mus musculus (mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49648.20

構造登録者

Langley, D.B.,Christ, D. (登録日: 2022-03-22, 公開日: 2022-06-29, 最終更新日: 2024-11-20)

主引用文献

Langley, D.B.,Schofield, P.,Nevoltris, D.,Jackson, J.,Jackson, K.J.L.,Peters, T.J.,Burk, M.,Matthews, J.M.,Basten, A.,Goodnow, C.C.,van Nunen, S.,Reed, J.H.,Christ, D.
Genetic and structural basis of the human anti-alpha-galactosyl antibody response.
Proc.Natl.Acad.Sci.USA, 119:e2123212119-e2123212119, 2022

PubMed Abstract: Humans lack the capacity to produce the Galα1-3Galβ1-4GlcNAc (α-gal) glycan, and produce anti-α-gal antibodies upon exposure to the carbohydrate on a diverse set of immunogens, including commensal gut bacteria, malaria parasites, cetuximab, and tick proteins. Here we use X-ray crystallographic analysis of antibodies from α-gal knockout mice and humans in complex with the glycan to reveal a common binding motif, centered on a germline-encoded tryptophan residue at Kabat position 33 (W33) of the complementarity-determining region of the variable heavy chain (CDRH1). Immunoglobulin sequencing of anti-α-gal B cells in healthy humans and tick-induced mammalian meat anaphylaxis patients revealed preferential use of heavy chain germline IGHV3-7, encoding W33, among an otherwise highly polyclonal antibody response. Antigen binding was critically dependent on the presence of the germline-encoded W33 residue for all of the analyzed antibodies; moreover, introduction of the W33 motif into naive IGHV3-23 antibody phage libraries enabled the rapid selection of α-gal binders. Our results outline structural and genetic factors that shape the human anti-α-galactosyl antibody response, and provide a framework for future therapeutics development.

PubMed: 35867757
DOI: 10.1073/pnas.2123212119

実験手法

X-RAY DIFFRACTION (1.55 Å)