6Q19

Inferred intermediate (I-6) of the human antibody lineage 652

6Q19 の概要

• エントリーDOI: 10.2210/pdb6q19/pdb
• 分子名称: Fab lambda chain, Fab heavy chain (3 entities in total)
• 機能のキーワード: antibody, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48661.93

構造登録者

McCarthy, K.R.,Harrison, S.C. (登録日: 2019-08-03, 公開日: 2019-12-18, 最終更新日: 2020-01-01)

主引用文献

McCarthy, K.R.,Raymond, D.D.,Do, K.T.,Schmidt, A.G.,Harrison, S.C.
Affinity maturation in a human humoral response to influenza hemagglutinin.
Proc.Natl.Acad.Sci.USA, 2019

PubMed Abstract: Affinity maturation of the B cell antigen receptor (BCR) is a conserved and crucial component of the adaptive immune response. BCR lineages, inferred from paired heavy- and light-chain sequences of rearranged Ig genes from multiple descendants of the same naive B cell precursor (the lineages' unmutated common ancestor, "UCA"), make it possible to reconstruct the underlying somatic evolutionary history. We present here an extensive structural and biophysical analysis of a lineage of BCRs directed against the receptor binding site (RBS) of subtype H1 influenza virus hemagglutinin (HA). The lineage includes 8 antibodies detected directly by sequencing, 3 in 1 principal branch and 5 in the other. When bound to HA, the heavy-chain third complementarity determining region (HCDR3) fits with an invariant pose into the RBS, but in each of the 2 branches, the rest of the Fab reorients specifically, from its position in the HA-bound UCA, about a hinge at the base of HCDR3. New contacts generated by the reorientation compensate for contacts lost as the H1 HA mutated during the time between the donor's initial exposure and the vaccination that preceded sampling. Our data indicate that a "pluripotent" naive response differentiated, in each branch, into 1 of its possible alternatives. This property of naive BCRs and persistence of multiple branches of their progeny lineages can offer broader protection from evolving pathogens than can a single, linear pathway of somatic mutation.

PubMed: 31843892
DOI: 10.1073/pnas.1915620116

実験手法

X-RAY DIFFRACTION (1.58 Å)