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

TY - JOUR

T1 - Structure of a group A streptococcal phage-encoded virulence factor reveals a catalytically active triple-stranded beta-helix

AU - Smith, N L

AU - Taylor, E J

AU - Lindsay, A M

AU - Charnock, S J

AU - Turkenburg, J P

AU - Dodson, E J

AU - Davies, G J

AU - Black, G W

PY - 2005/12/6

Y1 - 2005/12/6

N2 - 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-angstrom resolution, reveals an unusual triple-stranded beta-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 P-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 beta-helix is not simply a structural scaffold, as previously envisaged; it is harnessed to provide a 200-angstrom-long substrate-binding groove for the optimal reduction in hyaluronan viscosity to aid phage penetration of the capsule.

AB - 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-angstrom resolution, reveals an unusual triple-stranded beta-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 P-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 beta-helix is not simply a structural scaffold, as previously envisaged; it is harnessed to provide a 200-angstrom-long substrate-binding groove for the optimal reduction in hyaluronan viscosity to aid phage penetration of the capsule.

KW - crystal

KW - enzyme

KW - lyase

KW - streptococcus

KW - bacteriophage

KW - PYOGENES BACTERIOPHAGE H4489A

KW - HUMAN PHARYNGEAL CELLS

KW - SHORT TAIL FIBER

KW - CRYSTAL-STRUCTURE

KW - HYALURONATE LYASE

KW - GENOME SEQUENCE

KW - GENE

KW - PROTEIN

KW - OLIGOSACCHARIDES

KW - RESOLUTION

U2 - 10.1073/pnas.0504782102

DO - 10.1073/pnas.0504782102

M3 - Article

SN - 0027-8424

VL - 102

SP - 17652

EP - 17657

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 49

ER -