Crystal structure of the octameric pore of staphylococcal γ-hemolysin reveals the β-barrel pore formation mechanism by two components

Keitaro Yamashita, Yuka Kawai, Yoshikazu Tanaka, Nagisa Hirano, Jun Kaneko, Noriko Tomita, Makoto Ohta, Yoshiyuki Kamio, Min Yao, Isao Tanaka

Research output: Contribution to journalArticlepeer-review

111 Citations (Scopus)

Abstract

Staphylococcal γ-hemolysin is a bicomponent pore-forming toxin composed of LukF and Hlg2. These proteins are expressed as water-soluble monomers and then assemble into the oligomeric pore form on the target cell. Here, we report the crystal structure of the octameric pore form of γ-hemolysin at 2.5 Å resolution, which is the first high-resolution structure of a β-barrel transmembrane protein composed of two proteins reported to date. The octameric assembly consists of four molecules of LukF and Hlg2 located alternately in a circular pattern, which explains the biochemical data accumulated over the past two decades. The structure, in combination with the monomeric forms, demonstrates the elaborate molecular machinery involved in pore formation by two different molecules, in which interprotomer electrostatic interactions using loops connecting β2 and β3 (loop A: Asp43-Lys48 of LukF and Lys37-Lys43 of Hlg2) play pivotal roles as the structural determinants for assembly through unwinding of the N-terminal β-strands (aminolatch) of the adjacent protomer, releasing the transmembrane stem domain folded into a β-sheet in the monomer (prestem), and interaction with the adjacent protomer.

Original languageEnglish
Pages (from-to)17314-17319
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number42
DOIs
Publication statusPublished - 2011 Oct 18

ASJC Scopus subject areas

  • General

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