9MMX

M6 protein with Factor H 6-7 domain

Summary for 9MMX

• Entry DOI: 10.2210/pdb9mmx/pdb
• Descriptor: Complement factor H, M protein, serotype 6, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: complement evasion, factor h, m protein, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 68959.48

Authors

Kumar, A.,Ghosh, P. (deposition date: 2024-12-20, release date: 2026-02-04, Last modification date: 2026-05-20)

Primary citation

Kumar, A.,Wang, K.C.,Ghosh, P.
Structural mechanisms for the recruitment of factor H by Streptococcus pyogenes.
Structure, 34:778-, 2026

PubMed Abstract: The bacterial pathogen Streptococcus pyogenes (Strep A) recruits the complement regulator factor H (FH) to its surface using M proteins and FbaA. However, no conserved FH-binding sequence pattern is evident in these proteins. To address this, we determined the structures of M5 protein, M6 protein, and FbaA fragments complexed with FH domains 6 and 7. M5 and M6 proteins formed dimeric α-helical coiled coils, as expected, while FbaA formed a monomeric three-helix bundle preceded by a loop. Each Strep A protein had a different FH-binding mode, and distinct FH-binding sequence patterns were constructed for each based on substitution mutagenesis. About half of the known 250 Strep A strains were identified to have FH-binding patterns, with the majority due to FbaA as compared to M or M-like Enn proteins. Our structural and functional elucidation of the mechanism of FH recruitment is applicable to the precise investigation of its role in Strep A virulence.

PubMed: 41844154
DOI: 10.1016/j.str.2026.02.010

Experimental method

X-RAY DIFFRACTION (1.9 Å)