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Structural insights into the molecular organization of the S‐layer from Clostridium difficile
Author(s) -
Fagan Robert P.,
AlbesaJové David,
Qazi Omar,
Svergun Dmitri I.,
Brown Katherine A.,
Fairweather Neil F.
Publication year - 2009
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2009.06603.x
Subject(s) - biology , biogenesis , s layer , clostridium difficile , bacterial adhesin , peptide sequence , layer (electronics) , bacteria , microbiology and biotechnology , biochemistry , genetics , gene , virulence , nanotechnology , materials science , antibiotics
Summary Clostridium difficile expresses a surface layer (S‐layer) which coats the surface of the bacterium and acts as an adhesin facilitating interaction of the bacterium with host enteric cells. The S‐layer contains a high‐molecular‐weight S‐layer protein (HMW SLP) and its low‐molecular‐weight partner protein (LMW SLP). We show that these proteins form a tightly associated non‐covalent complex, the H/L complex, and we identify the regions of both proteins responsible for complex formation. The 2.4 Å X‐ray crystal structure of a truncated derivative of the LMW SLP reveals two domains. Domain 1 has a two‐layer sandwich architecture while domain 2, predicted to orientate towards the external environment, contains a novel fold. Small‐angle X‐ray scattering analysis of the H/L complex shows an elongated molecule, with the two SLPs arranged ‘end‐to‐end’ interacting with each other through a small contact area. Alignment of LMW SLPs, which exhibit high sequence diversity, reveals a core of conserved residues that could reflect functional conservation, while allowing for immune evasion through sequence variation. These structures are the first described for the S‐layer of a bacterial pathogen, and provide insights into the assembly and biogenesis of the S‐layer.