Structure of a group A streptococcal phage-encoded virulence factor reveals a catalytically active triple-stranded beta-helix

Smith, Nicola, Taylor, Edward, Black (née Lindsay), Anna, Charnock, Simon, Turkenburg, Johan, Dodson, Eleanor, Davies, Gideon and Black, Gary (2005) Structure of a group A streptococcal phage-encoded virulence factor reveals a catalytically active triple-stranded beta-helix. Proceedings of the National Academy of Sciences of the United States of America, 102 (49). pp. 17652-17657. ISSN 0027-8424

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Abstract

Streptococcus pyogenes (group A Streptococcus) causes severe invasive infections including scarlet fever, pharyngitis (streptococcal sore throat), skin infections, necrotizing fasciitis (flesh-eating disease), septicemia, erysipelas, cellulitis, acute rheumatic fever, and toxic shock. The conversion from nonpathogenic to toxigenic strains of S. pyogenes is frequently mediated by bacteriophage infection. One of the key bacteriophage-encoded virulence factors is a putative “hyaluronidase,” HylP1, a phage tail-fiber protein responsible for the digestion of the S. pyogenes hyaluronan capsule during phage infection. Here we demonstrate that HylP1 is a hyaluronate lyase. The 3D structure, at 1.8-Å resolution, reveals an unusual triple-stranded β-helical structure and provides insight into the structural basis for phage tail assembly and the role of phage tail proteins in virulence. Unlike the triple-stranded β-helix assemblies of the bacteriophage T4 injection machinery and the tailspike endosialidase of the Escherichia coli K1 bacteriophage K1F, HylP1 possesses three copies of the active center on the triple-helical fiber itself without the need for an accessory catalytic domain. The triple-stranded β-helix is not simply a structural scaffold, as previously envisaged; it is harnessed to provide a 200-Å-long substrate-binding groove for the optimal reduction in hyaluronan viscosity to aid phage penetration of the capsule.

Item Type:	Article
Additional Information:	Devised and supervised part of the experimental work and co-wrote the paper. This work revealed that the core of a group A streptococcal phage-encoded hyaluronate lyase was comprised of a catalytically active triple-stranded beta-helix; a unique finding.
Subjects:	A100 Pre-clinical Medicine
Department:	Faculties > Health and Life Sciences > Applied Sciences
Related URLs:	Library Catalogue
Depositing User:	EPrint Services
Date Deposited:	07 May 2008 14:02
Last Modified:	20 May 2021 15:04
URI:	http://nrl.northumbria.ac.uk/id/eprint/2208

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