An M protein coiled coil unfurls and exposes its hydrophobic core to capture LL-37

eLife

Kuei-Chen Wang¹  Partho Ghosh¹  Piotr Kolesinski¹  Victor Nizet²  Yujiro Hirose² 

[1] Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, United States;Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, United States;

关键词: coiled coils;    Streptococcus pyogenes;    M protein;    antimicrobial peptide;    cathelicidin;    LL-37;   

DOI  :  10.7554/eLife.77989

来源: DOAJ

【 摘 要 】

Surface-associated, coiled-coil M proteins of Streptococcus pyogenes (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.

【 授权许可】

Unknown