Genetic and biochemical analysis of human Peptidoglycan Recognition Protein-S

Oliver, Shune
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Peptidoglycan Recognition Proteins (PGRPs) are a family of conserved proteins with antimicrobial activity in humans. PGRP-S is a 20kDA monomer with a poorly elucidated bactericidal mechanism. The aim of this project was to examine the genetic variation of the PGRP-S gene in the Sub-Saharan African immunocompromised population. DNA was extracted from the blood of HIV positive patients with and without active Tuberculosis as well as healthy controls. The coding regions of PGRP-S were amplified and subjected to direct automated sequencing. A wild type PGRP-S GST fusion protein was cloned, overexpressed, purified and used to determine protein-protein interactions as well as used in antimicrobial assays. Three polymorphic sites were noted in the population, as well as a stable variation in the genomic DNA from the mRNA sequence. One HIV positive Venda patient had a potentially novel non-synonymous mutation which would lead to a variant of protein with a reduced capacity to bind peptidoglycan. The variation of the genomic DNA to its corresponding nucleotide in the mRNA at position 80 may represent an example of RNA editing. The protein cloned had no discernable activity. Further studies with a larger population group and further analysis of the non-synonymous mutant protein may yield insight on the genetics and biochemistry of PGRP-S.