7SAF

Fragment of streptococcal M87 protein fused to GCN4 adaptor

Summary for 7SAF

• Entry DOI: 10.2210/pdb7saf/pdb
• Descriptor: General control transcription factor GCN4/M protein chimera, PHOSPHATE ION (3 entities in total)
• Functional Keywords: coiled-coil, virulence factor, cell adhesion
• Biological source: Saccharomyces cerevisiae (Baker's yeast); More
• Total number of polymer chains: 2
• Total formula weight: 17275.07

Authors

Kolesinski, P.,Ghosh, P. (deposition date: 2021-09-22, release date: 2022-07-13, Last modification date: 2023-10-18)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.45 Å)