The crystal structure of filamentous hemagglutinin secretion domain and its implications for the two-partner secretion pathway
AUTOR(ES)
Clantin, Bernard
FONTE
National Academy of Sciences
RESUMO
Filamentous hemagglutinin (FHA), the major 230-kDa adhesin of the whooping cough agent Bordetella pertussis, is one of the most efficiently secreted proteins in Gram-negative bacteria. FHA is secreted by means of the two-partner secretion (TPS) pathway. Several important human, animal, and plant pathogens also secrete adhesins and other virulence factors by using this mode of secretion. A TPS system is composed of two separate proteins, with TpsA the secreted protein and TpsB its associated specific outermembrane transporter. All TPS-secreted proteins contain a distinctive N-proximal module essential for secretion, the TPS domain. We report here the 1.7- Å structure of a functionally secreted 30-kDa N-terminal fragment of FHA. It reveals that the TPS domain folds into a β-helix, with three extrahelical motifs, a β-hairpin, a four-stranded β-sheet, and an N-terminal capping, mostly formed by the nonconserved regions of the TPS domain. The structure thus explains why the TPS domain is able to initiate folding of the β-helical motifs that form the central domain of the adhesin, because it is itself a β-helical scaffold. It also contains less conserved extrahelical regions most likely involved in specific properties, such as the recognition of the outer-membrane transporter. This structure is representative of the TPS domains found so far in >100 secreted proteins from pathogenic bacteria. It also provides a mechanistic insight into how protein folding may be linked to secretion in the TPS pathway.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=395945Documentos Relacionados
- The PhlA Hemolysin from the Entomopathogenic Bacterium Photorhabdus luminescens Belongs to the Two-Partner Secretion Family of Hemolysins
- Crystal structure of CATGGCCATG and its implications for A-tract bending models.
- The crystal structure of the signature domain of cartilage oligomeric matrix protein: implications for collagen, glycosaminoglycan and integrin binding
- Structure of a two-domain fragment of HIV-1 integrase: implications for domain organization in the intact protein
- Crystal structure of the S-adenosylmethionine-dependent enzyme MoaA and its implications for molybdenum cofactor deficiency in humans
