7SAY

Fragment of streptococcal M87 protein fused to GCN4 adaptor in complex with human cathelicidin

7SAY の概要

• エントリーDOI: 10.2210/pdb7say/pdb
• 分子名称: General control transcription factor GCN4/M protein chimera, Antibacterial peptide LL-37, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: complex, virulence factor, antimicrobial peptide, immune system
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 43427.23

構造登録者

Kolesinski, P.,Ghosh, P. (登録日: 2021-09-23, 公開日: 2022-07-13, 最終更新日: 2023-10-18)

主引用文献

Kolesinski, P.,Wang, K.C.,Hirose, Y.,Nizet, V.,Ghosh, P.,Stallings, C.L.,Dotsch, V.
An M protein coiled coil unfurls and exposes its hydrophobic core to capture LL-37
Elife, 11:-, 2022

PubMed Abstract: Surface-associated, coiled-coil M proteins of (Strep A) disable human immunity through interaction with select proteins. However, coiled coils lack features typical of protein-protein interaction sites, and it is therefore challenging to understand how M proteins achieve specific binding, for example, with the human antimicrobial peptide LL-37, leading to its neutralization. The crystal structure of a complex of LL-37 with M87 protein, an antigenic M protein variant from a strain that is an emerging threat, revealed a novel interaction mode. The M87 coiled coil unfurled and asymmetrically exposed its hydrophobic core to capture LL-37. A single LL-37 molecule was bound by M87 in the crystal, but in solution additional LL-37 molecules were recruited, consistent with a 'protein trap' neutralization mechanism. The interaction mode visualized crystallographically was verified to contribute significantly to LL-37 resistance in an M87 Strep A strain and was identified to be conserved in a number of other M protein types that are prevalent in human populations. Our results provide specific detail for therapeutic inhibition of LL-37 neutralization by M proteins.

PubMed: 35726694
DOI: 10.7554/eLife.77989

実験手法

X-RAY DIFFRACTION (2.1 Å)