Functional similarities between the dictyostelium protein AprA and the human protein dipeptidyl‐peptidase IV. (15th February 2017)

• Record Type: Journal Article
• Authors: Herlihy, Sarah E.; Tang, Yu; Phillips, Jonathan E.; Gomer, Richard H.
• Is Part Of: Protein science. Volume 26:Number 3(2017)
• Page Start: 578
• Page End: 585
• Publication Date: 2017-02-15
• Subjects: AprA -- DPPIV -- structure similarity -- functional similarity -- protease -- chemorepellent; Proteins -- Periodicals; 572.6
• DOI: 10.1002/pro.3107
• Languages: English
• ISSNs: 0961-8368

Abstract

Abstract: Autocrine proliferation repressor protein A (AprA) is a protein secreted by Dictyostelium discoideum cells. Although there is very little sequence similarity between AprA and any human protein, AprA has a predicted structural similarity to the human protein dipeptidyl peptidase IV (DPPIV). AprA is a chemorepellent for Dictyostelium cells, and DPPIV is a chemorepellent for neutrophils. This led us to investigate if AprA and DPPIV have additional functional similarities. We find that like AprA, DPPIV is a chemorepellent for, and inhibits the proliferation of, D. discoideum cells, and that AprA binds some DPPIV binding partners such as fibronectin. Conversely, rAprA has DPPIV‐like protease activity. These results indicate a functional similarity between two eukaryotic chemorepellent proteins with very little sequence similarity, and emphasize the usefulness of using a predicted protein structure to search a protein structure database, in addition to searching for proteins with similar sequences.