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Protein Domain : Pertactin virulence factor family

Primary Identifier  IPR003991 Type  Family
Short Name  Pertactin_virulence_factor
description  Bordetella pertussis is a Gram-negative, aerobic coccobacillus that causes pertussis (whooping cough), especially in young children []. Once present in the lungs, the bacterium attaches to ciliated pulmonary epithelial cells via a collection of outer membrane proteins, all of which are virulence factors.Pertactin, or P69 protein, is one of these virulence factors. Pertactin andfilamentous haemagglutinin have been identified as Bordetella adhesins []. Both proteins contain an arg-gly-asp (RGD) motif that promotes binding to integrins, known to be important in cell mobility and development. Theproduction of most Bordetella virulence factors (including pertactin) is controlled by a two-component signal transduction system, comprising theBvgA regulator and the BvgS sensor []. Pertactin shares a high level of similarity with other Bordetella adhesins, such as BrkA. The protein isfirst produced as a 93kDa precursor. Upon secretion into the extracellularenvironment, a 30kDa domain at the C terminus remains in the outer membrane,while the mature 60.4kDa pertactin molecule is released [].The crystal structure of mature pertactin has been determined to 2.5A resolution by means of X-ray diffraction. The fold is characterised by a 16-stranded parallel β-helix, with a V-shaped cross-section. Several between-strand amino-acid repeats form internal and external ladders. The helical structure is interrupted by several protruding loops that contain motifs associated with the activity of the protein. One such sequence - [GGXXP]5 - appears directly after the RGD motif, and may mediate interaction with epithelial cells. The C-terminal region of P.69 pertactin contains a [PQP]5 motif loop, which contains the major immunoprotective epitope [].The tcfA gene of B. pertussis encodes a unique virulence-associated factor, Tcf (tracheal colonisation factor) []. The derived amino acid sequence of tcfA predicts a 68kDa RGD-containing, proline-rich protein.Amino acid sequence analysis reveals that the C-terminal 30kDa of this protein shares ~50% identity with the 30kDa C terminus of the Bordetella pertactin precursor.The Bordetella resistance to killing, brk, locus has cloned and sequencedand found to encode two divergently transcribed open reading frames (ORFs),designated BrkA and BrkB []. Both ORFs are necessary for serum resistance. BrkA shares ~29% identity with pertactin and contains two RGD motifs, in addition to a proteolytic processing site and an outer membrane targeting signal. BrkA, like pertactin, is involved in adherence and invasion.

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