Role of Non-local Interactions between CDR Loops in Binding Affinity of MR78 Antibody to Marburg Virus Glycoprotein

Amandeep K. Sangha, Jinhui Dong, Lauren Williamson, Takao Hashiguchi, Erica Ollmann Saphire, James E. Crowe, Jens Meiler

研究成果: Contribution to journalArticle査読

4 被引用数 (Scopus)

抄録

An atomic-detail model of the Marburg virus glycoprotein in complex with a neutralizing human monoclonal antibody designated MR78 was constructed using Phenix.Rosetta starting from a 3.6Å crystallographic density map. The Asp at T6 in the HCDR3's bulged torso cannot form the canonical salt bridge as position T2 lacks an Arg or Lys residue. It instead engages in a hydrogen bond interaction with a Tyr contributed by the HCDR1 loop. This inter-CDR loop interaction stabilizes the bulged conformation needed for binding to the viral glycoprotein: a Tyr to Phe mutant displays a binding affinity reduced by a factor of at least 10. We found that 5% of a database of 465 million human antibody sequences has the same residues at T2 and T6 positions in HCDR3 and Tyr in HCDR1 that could potentially form this Asp-Tyr interaction, and that this interaction might contribute to a non-canonical bulged torso conformation. Sangha et al. have discovered that the conformation of the human antibody MR78 HCDR3 loop that binds to Marburg virus glycoprotein is stabilized by a non-local hydrogen bond between an Asp at T6 position of HCDR3 and a Tyr in HCDR1.

本文言語英語
ページ(範囲)1820-1828.e2
ジャーナルStructure
25
12
DOI
出版ステータス出版済み - 12 5 2017

All Science Journal Classification (ASJC) codes

  • 構造生物学
  • 分子生物学

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