8T51

Crystal structure of Fab 3.10C2 bound to TREM2

8T51 の概要

• エントリーDOI: 10.2210/pdb8t51/pdb
• 分子名称: 3.10C2 Fab heavy chain, 3.10C2 Fab light chain, Triggering receptor expressed on myeloid cells 2 peptide, ... (9 entities in total)
• 機能のキーワード: antibody, fab, peptide binding protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 102728.02

構造登録者

Hsu, P.L.,Wallweber, H. (登録日: 2023-06-12, 公開日: 2024-06-19, 最終更新日: 2024-10-09)

主引用文献

Hsiao, Y.C.,Wallweber, H.A.,Alberstein, R.G.,Lin, Z.,Du, C.,Etxeberria, A.,Aung, T.,Shang, Y.,Seshasayee, D.,Seeger, F.,Watkins, A.M.,Hansen, D.V.,Bohlen, C.J.,Hsu, P.L.,Hotzel, I.
Rapid affinity optimization of an anti-TREM2 clinical lead antibody by cross-lineage immune repertoire mining.
Nat Commun, 15:8382-8382, 2024

PubMed Abstract: We describe a process for rapid antibody affinity optimization by repertoire mining to identify clones across B cell clonal lineages based on convergent immune responses where antigen-specific clones with the same heavy (V) and light chain germline segment pairs, or parallel lineages, bind a single epitope on the antigen. We use this convergence framework to mine unique and distinct V lineages from rat anti-triggering receptor on myeloid cells 2 (TREM2) antibody repertoire datasets with high diversity in the third complementarity-determining loop region (CDR H3) to further affinity-optimize a high-affinity agonistic anti-TREM2 antibody while retaining critical functional properties. Structural analyses confirm a nearly identical binding mode of anti-TREM2 variants with subtle but significant structural differences in the binding interface. Parallel lineage repertoire mining is uniquely tailored to rationally explore the large CDR H3 sequence space in antibody repertoires and can be easily and generally applied to antibodies discovered in vivo.

PubMed: 39333507
DOI: 10.1038/s41467-024-52442-y

実験手法

X-RAY DIFFRACTION (1.9 Å)