User:MarissaAllen/Pertactin

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In molecular biology, pertactin (PRN) is a highly immunogenic virulence factor of Bordetella pertussis, the bacterium that causes pertussis. It was originally known as P.69, referring to its relative molecular mass of 69,000.[1] Specifically, it is an outer membrane protein that promotes adhesion to tracheal epithelial cells. PRN is purified from Bordetella pertussis and is used for the vaccine production as one of the important components of acellular pertussis vaccine.

Pertactin is a single domain, folded, monomer mostly consisting of three-strand beta helical structures. Like other binding proteins, pertactin, has proline-rich regions (PRRs) that provide binding sites on the protein. Pertactin has 2 PRRs, one following an RGD sequence and the other in located in the C-terminal. The C-terminal site contains a PQP motif and is immunodominant.[1] At the C-terminus there are 2, two-stranded beta rolls that extend and are variable. [1] A large part of the N-terminus of the pertactin protein is composed of beta helix repeats. This region of the pertactin protein is secreted through the C-terminal autotransporter. The N-terminal signal sequences promotes the secretion of PRN into the periplasm through the bacterial secretion system (Sec) and consequently, the translocation into the outer membrane where it is proteolytically cleaved. The loops in the right handed β-helix of the N-terminus that protrudes out of cell surface (region R1) contains sequence repeats Gly-Gly-Xaa-Xaa-Pro and the RGD domain Arg-Gly-Asp. This RGD domain allows PRN to function as an adhesin and invasin, binding to integrins on the outer membrane of the cell. Another loop of the extending β-helix is region 2 (R2) which contains Pro-Gln-Pro (PQP) repeats towards the C-terminus. This protein’s contribution to immunity is still premature. Reports suggest that R1 and R2 are immunogenic regions, however, recent studies regarding genetic variation of those regions prove otherwise.

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In B.bronchiseptica

Pertactin adheres to only ciliated epithelial cells of B. bronchiseptica in vivo. However, in vitro, PRN does not adhere to either. PRN does however help provide resistance towards a hyperinflammatory response of innate immunity for B. bronchiseptica. With respect to the adaptive immunity, studies show that PRN plays a role in combating neutrophil-mediated clearance of B. bronchiseptica.

Genetics

The gene that encodes pertactin is CN2992. It is rich in guanine and cytosine nucleobases and encodes a protein made of 910 amino acids. This full protein has a molecular weight of 93,478 Da. This suggests that pertactin is processed from this larger protein. After processing pertactin ends at its’ final weight of 69kDa. Pertactin is a vir-regulated outer membrane protein. There is speculation that the gene for pertactin evolved separately from the metabolic genes of B. pertussis.[2] There are 2 RGD sequences in the genetic code of B. pertussis. The residues of these proteins are found at position 225-227 and the second is at position 665-667. The amino-terminal RGD is associated with cell binding. The carboxyl-terminal RGD is not shown to be involved with binding to mammalian cells however. [3]

Bordetella pertussis strains with deficient pertactin

Pertactin is a common addition in acellular vaccines against B. pertussis. Unfortunately, even with high vaccination rates whooping cough continues to spread in communities around the world. [4] In recent years a new strain of B. pertussis has emerged, PRN deficient. [4] In the United States PRN deficient strains account for 85% of whooping cough cases. [4] PRN is the only component in acellular vaccines that is closely associated with the outer membrane. It was shown that antibodies against PRN remain higher for a longer period that other components in the acellular vaccine. There are 3 parts of PRN that may contribute to its selective loss: functional redundancy, longer functional resistance of antibodies, and its close association with the membrane surface.[4] Theses specific traits of PRN cause it to be a target of selective loss because of how antibodies would be able to recognize PRN due to its location on the outer membrane. By no longer producing PRN bacterium may be able to evade the host immune system for a longer period of time because antibodies are likely associated with PRN. PRN also serves the same purpose as other outer membrane proteins making it less essential for a cell to produce.