Researchers discovered that a protein on the surface of the strep throat bacteria can unfold and grab the human antimicrobial peptide LL‑37, effectively neutralizing it. This binding can happen with multiple LL‑37 molecules and is seen in several common bacterial strains, suggesting a clever way the bacteria dodge our immune defenses.

Surface-associated, coiled-coil M proteins of <i>Streptococcus pyogenes</i> (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.