RRC ID 59326
著者 Chen YZ, Klöditz K, Lee ES, Nguyen DP, Yuan Q, Johnson J, Lee-Yow Y, Hall A, Mitani S, Xia NS, Fadeel B, Xue D.
タイトル Structure and function analysis of the C. elegans aminophospholipid translocase TAT-1.
ジャーナル J Cell Sci
Abstract The Caenorhabditis elegans aminophospholipid translocase TAT-1 maintains phosphatidylserine (PS) asymmetry in the plasma membrane and regulates endocytic transport. Despite these important functions, the structure-function relationship of this protein is poorly understood. Taking advantage of the tat-1 mutations identified by the C. elegans million mutation project, we investigated the effects of 16 single amino acid substitutions on the two functions of the TAT-1 protein. Two substitutions that alter a highly conserved PISL motif in the fourth transmembrane domain and a highly conserved DKTGT phosphorylation motif, respectively, disrupt both functions of TAT-1, leading to a vesicular gut defect and ectopic PS exposure on the cell surface, whereas most other substitutions across the TAT-1 protein, often predicted to be deleterious by bioinformatics programs, do not affect the functions of TAT-1. These results provide in vivo evidence for the importance of the PISL and DKTGT motifs in P4-type ATPases and improve our understanding of the structure-function relationship of TAT-1. Our study also provides an example of how the C. elegans million mutation project helps decipher the structure, functions, and mechanisms of action of important genes.
巻・号 132(5)
公開日 2019-2-28
DOI 10.1242/jcs.227660
PII jcs.227660
PMID 30683797
PMC PMC6432707
MeSH Amino Acid Motifs / genetics Animals Animals, Genetically Modified Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Computational Biology Endocytosis Intestines / physiology* Mutation / genetics Phenotype Phospholipid Transfer Proteins / genetics Phospholipid Transfer Proteins / metabolism* Protein Conformation Protein Transport Structure-Activity Relationship
IF 4.517
引用数 0
リソース情報
線虫 tm3117