Methods for the Prediction of Cleavage Sites of the Polypeptide in Certain Proteins

Abstract

Many proteins critical to the existence of parasites from infectious agents that affect man, including malaria, leishmania, and trypansoma, are attached to the surface membrane by glycosyl-phosphatidyl inositol (GPI) anchors. Creation of GPI-anchored proteins involves elimination of a bond between adjacent amino acids in a newly formed, or nascent, polypeptide and attachment of a GPI anchor at this site. Because interfering with this process by altering the location of attachment is a potential infection-control strategy in humans, knowledge of the cleavage site in the nascent polypeptide is important. Determination of the cleavage point directly through biochemical analysis is both labor and resource intensive. We develop both likelihood-based and Bayesian approaches for use in the identification of the site of cleavage of GPI-anchored proteins. These methods are demonstrated using four examples where extensive biochemical analyses already have identified the bond in the newly formed polypeptide where a GPI anchor is attached. In contrast to sole reliance on biochemical analyses, use of the proposed methods has great potential for savings of both time and money.