The conformation and function of a multimodular glycogen-degrading pneumococcal virulence factor

Structure. 2011 May 11;19(5):640-51. doi: 10.1016/j.str.2011.03.001.

Abstract

SpuA is a large multimodular cell wall-attached enzyme involved in the degradation of glycogen by the pathogenic bacterium Streptococcus pneumoniae. The deletion of the gene encoding SpuA from the bacterium resulted in a strain with reduced competitiveness in a mouse model of virulence relative to the parent strain, linking the degradation of host-glycogen to the virulence of the bacterium. Through the combined use of X-ray crystallography, small-angle X-ray scattering, and inhibitor binding, the molecular features involved in substrate recognition by this complex protein are revealed. This uniquely illustrates the complexity of the active site, the conformational changes incurred during carbohydrate binding by this protein, and the interaction and cooperation of its composite modules during this process. New insight into the function of this particular pneumococcal virulence factor is provided along with substantial contributions to the nascent framework for understanding the structural and functional interplay between modules in multimodular carbohydrate-active enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Cell Line, Tumor
  • Cell Wall / chemistry
  • Cell Wall / metabolism
  • Crystallography, X-Ray
  • Glycogen* / metabolism
  • Glycoside Hydrolases / chemistry*
  • Glycoside Hydrolases / genetics
  • Glycoside Hydrolases / metabolism
  • Humans
  • Lung / microbiology
  • Mice
  • Mice, Inbred Strains
  • Models, Molecular
  • Multiprotein Complexes / chemistry*
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Pneumococcal Infections / microbiology*
  • Pneumococcal Infections / pathology
  • Protein Binding
  • Protein Conformation
  • Recombinant Proteins / chemistry*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Scattering, Small Angle
  • Streptococcus pneumoniae* / chemistry
  • Streptococcus pneumoniae* / metabolism
  • Streptococcus pneumoniae* / pathogenicity
  • Virulence
  • Virulence Factors / chemistry*
  • Virulence Factors / genetics
  • Virulence Factors / metabolism

Substances

  • Bacterial Proteins
  • Multiprotein Complexes
  • Recombinant Proteins
  • Virulence Factors
  • Glycogen
  • Glycoside Hydrolases

Associated data

  • PDB/2YA0
  • PDB/2YA1
  • PDB/2YA2