Herlihy Sarah E, Tang Yu, Phillips Jonathan E, Gomer Richard H
Department of Biology, Texas A&M University, College Station, Texas.
Protein Sci. 2017 Mar;26(3):578-585. doi: 10.1002/pro.3107. Epub 2017 Feb 15.
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.
自分泌增殖抑制蛋白A（AprA）是一种由盘基网柄菌细胞分泌的蛋白质。尽管AprA与任何人类蛋白质之间的序列相似性非常低，但AprA与人类蛋白质二肽基肽酶IV（DPPIV）在预测的结构上具有相似性。AprA是盘基网柄菌细胞的一种化学排斥剂，而DPPIV是中性粒细胞的一种化学排斥剂。这促使我们研究AprA和DPPIV是否还有其他功能相似性。我们发现，与AprA一样，DPPIV是盘基网柄菌细胞的化学排斥剂，并能抑制其增殖，而且AprA能结合一些DPPIV的结合伴侣，如纤连蛋白。相反，重组AprA具有类似DPPIV的蛋白酶活性。这些结果表明，两种序列相似性很低的真核生物化学排斥蛋白之间存在功能相似性，并强调了除了搜索具有相似序列的蛋白质外，利用预测的蛋白质结构搜索蛋白质结构数据库的有用性。
