9CNW

CryoEM structure of the APO-BAM complex in DDM detergent

9CNW の概要

• エントリーDOI: 10.2210/pdb9cnw/pdb
• EMDBエントリー: 45764
• 分子名称: Outer membrane protein assembly factor BamA, Outer membrane protein assembly factor BamB, Outer membrane protein assembly factor BamC, ... (5 entities in total)
• 機能のキーワード: membrane protein, protein structure
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 210826.21

構造登録者

Sun, D.,Tegunov, D.,Payandeh, J. (登録日: 2024-07-15, 公開日: 2024-12-25)

主引用文献

Sun, D.,Storek, K.M.,Tegunov, D.,Yang, Y.,Arthur, C.P.,Johnson, M.,Quinn, J.G.,Liu, W.,Han, G.,Girgis, H.S.,Alexander, M.K.,Murchison, A.K.,Shriver, S.,Tam, C.,Ijiri, H.,Inaba, H.,Sano, T.,Yanagida, H.,Nishikawa, J.,Heise, C.E.,Fairbrother, W.J.,Tan, M.W.,Skelton, N.,Sandoval, W.,Sellers, B.D.,Ciferri, C.,Smith, P.A.,Reid, P.C.,Cunningham, C.N.,Rutherford, S.T.,Payandeh, J.
The discovery and structural basis of two distinct state-dependent inhibitors of BamA.
Nat Commun, 15:8718-8718, 2024

PubMed Abstract: BamA is the central component of the essential β-barrel assembly machine (BAM), a conserved multi-subunit complex that dynamically inserts and folds β-barrel proteins into the outer membrane of Gram-negative bacteria. Despite recent advances in our mechanistic and structural understanding of BamA, there are few potent and selective tool molecules that can bind to and modulate BamA activity. Here, we explored in vitro selection methods and different BamA/BAM protein formulations to discover peptide macrocycles that kill Escherichia coli by targeting extreme conformational states of BamA. Our studies show that Peptide Targeting BamA-1 (PTB1) targets an extracellular divalent cation-dependent binding site and locks BamA into a closed lateral gate conformation. By contrast, PTB2 targets a luminal binding site and traps BamA into an open lateral gate conformation. Our results will inform future antibiotic discovery efforts targeting BamA and provide a template to prospectively discover modulators of other dynamic integral membrane proteins.

PubMed: 39379361
DOI: 10.1038/s41467-024-52512-1

実験手法

ELECTRON MICROSCOPY (2.6 Å)