5HYT
Structure of human C4b-binidng protein alpha chain CCP domains 1 and 2 in complex with the hypervariable region of group A Streptococcus M22 protein
Summary for 5HYT
| Entry DOI | 10.2210/pdb5hyt/pdb |
| Related | 5HYP 5HYU 5HZP 5I0Q |
| Descriptor | Precursor to Protein Sir22, C4b-binding protein alpha chain (3 entities in total) |
| Functional Keywords | m protein, complement, streptococcus pyogenes, hypervariable antigen, immune system |
| Biological source | Streptococcus pyogenes More |
| Total number of polymer chains | 8 |
| Total formula weight | 96118.82 |
| Authors | Buffalo, C.Z.,Bahn-Suh, A.J.,Ghosh, P. (deposition date: 2016-02-01, release date: 2016-07-20, Last modification date: 2024-10-23) |
| Primary citation | Buffalo, C.Z.,Bahn-Suh, A.J.,Hirakis, S.P.,Biswas, T.,Amaro, R.E.,Nizet, V.,Ghosh, P. Conserved patterns hidden within group A Streptococcus M protein hypervariability recognize human C4b-binding protein. Nat Microbiol, 1:16155-16155, 2016 Cited by PubMed Abstract: No vaccine exists against group A Streptococcus (GAS), a leading cause of worldwide morbidity and mortality. A severe hurdle is the hypervariability of its major antigen, the M protein, with >200 different M types known. Neutralizing antibodies typically recognize M protein hypervariable regions (HVRs) and confer narrow protection. In stark contrast, human C4b-binding protein (C4BP), which is recruited to the GAS surface to block phagocytic killing, interacts with a remarkably large number of M protein HVRs (apparently ∼90%). Such broad recognition is rare, and we discovered a unique mechanism for this through the structure determination of four sequence-diverse M proteins in complexes with C4BP. The structures revealed a uniform and tolerant 'reading head' in C4BP, which detected conserved sequence patterns hidden within hypervariability. Our results open up possibilities for rational therapies that target the M-C4BP interaction, and also inform a path towards vaccine design. PubMed: 27595425DOI: 10.1038/nmicrobiol.2016.155 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.54 Å) |
Structure validation
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