Structural insights into the molecular organization of the S-layer from Clostridium difficile

被引:102
作者
Fagan, Robert P. [1 ]
Albesa-Jove, David [1 ]
Qazi, Omar [1 ]
Svergun, Dmitri I. [2 ,3 ]
Brown, Katherine A. [1 ]
Fairweather, Neil F. [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Ctr Mol Microbiol & Infect, Div Cell & Mol Biol, London SW7 2AZ, England
[2] Hamburg Outstat, European Mol Biol Lab, D-22603 Hamburg, Germany
[3] Russian Acad Sci, Inst Crystallog, Moscow, Russia
基金
英国生物技术与生命科学研究理事会;
关键词
GRAM-POSITIVE BACTERIA; SMALL-ANGLE SCATTERING; CELL-SURFACE PROTEINS; BIOLOGICAL MACROMOLECULES; WALL POLYMERS; RESOLUTION; BINDING; ADHERENCE; SOFTWARE; SEQUENCE;
D O I
10.1111/j.1365-2958.2009.06603.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 angstrom 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.
引用
收藏
页码:1308 / 1322
页数:15
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