Streptococcal M protein: Structural studies of the hypervariable region, free and bound to human C4BP

Ingemar André, J Persson, AM Blom, H Nilsson, Torbjörn Drakenberg, Gunnar Lindahl, Sara Linse

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

29 Citeringar (SciVal)

Sammanfattning

Streptococcus pyogenes is a Gram-positive bacterium that causes several diseases, including acute tonsillitis and toxic shock syndrome. The surface-localized M protein, which is the most extensively studied virulence factor of S. pyogenes, has an similar to 50-residue N-terminal hypervariable region (HVR) that plays a key role in the escape of the host immunity. Despite the extensive sequence variability in this region, many HVRs specifically bind human C4b-binding protein (C4BP), a plasma protein that inhibits complement activation. Although the more conserved parts of M protein are known to have dimeric coiled-coil structure, it is unclear whether the HVR also is a coiled coil. Here, we use nuclear magnetic resonance (NMR) to study the conformational properties of HVRs from M4 and M22 proteins in isolation and in complex with the M protein binding portion of C4BP. We conclude that the HVRs of M4 and M22 are folded as coiled coils and that the folded nucleus of the M4 HVR has a length of similar to 27 residues. Moreover, we demonstrate that the C4BP binding surface of M4-N is found within a region of four heptad repeats. Using molecular modeling, we propose a model for the structure of the M4 HVR that is consistent with our experimental information from NMR spectroscopy.
Originalspråkengelska
Sidor (från-till)4559-4568
TidskriftBiochemistry
Volym45
Utgåva14
DOI
StatusPublished - 2006

Ämnesklassifikation (UKÄ)

  • Biokemi och molekylärbiologi

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