7BM5

Crystal structure of Fab1, the Fab fragment of the anti-BamA monoclonal antibody MAB1

7BM5 の概要

• エントリーDOI: 10.2210/pdb7bm5/pdb
• 分子名称: Fab1 light chain, Fab1 heavy chain (2 entities in total)
• 機能のキーワード: antibody, antibiotic, fab, bama, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 288863.29

構造登録者

White, P.,Storek, K.M.,Rutherford, S.T.,Radford, S.E. (登録日: 2021-01-19, 公開日: 2021-06-02, 最終更新日: 2024-10-16)

主引用文献

White, P.,Haysom, S.F.,Iadanza, M.G.,Higgins, A.J.,Machin, J.M.,Whitehouse, J.M.,Horne, J.E.,Schiffrin, B.,Carpenter-Platt, C.,Calabrese, A.N.,Storek, K.M.,Rutherford, S.T.,Brockwell, D.J.,Ranson, N.A.,Radford, S.E.
The role of membrane destabilisation and protein dynamics in BAM catalysed OMP folding.
Nat Commun, 12:4174-4174, 2021

PubMed Abstract: The folding of β-barrel outer membrane proteins (OMPs) in Gram-negative bacteria is catalysed by the β-barrel assembly machinery (BAM). How lateral opening in the β-barrel of the major subunit BamA assists in OMP folding, and the contribution of membrane disruption to BAM catalysis remain unresolved. Here, we use an anti-BamA monoclonal antibody fragment (Fab1) and two disulphide-crosslinked BAM variants (lid-locked (LL), and POTRA-5-locked (P5L)) to dissect these roles. Despite being lethal in vivo, we show that all complexes catalyse folding in vitro, albeit less efficiently than wild-type BAM. CryoEM reveals that while Fab1 and BAM-P5L trap an open-barrel state, BAM-LL contains a mixture of closed and contorted, partially-open structures. Finally, all three complexes globally destabilise the lipid bilayer, while BamA does not, revealing that the BAM lipoproteins are required for this function. Together the results provide insights into the role of BAM structure and lipid dynamics in OMP folding.

PubMed: 34234105
DOI: 10.1038/s41467-021-24432-x

実験手法

X-RAY DIFFRACTION (2.95 Å)