caa a22 4500 477127452 CHVBK 20180405111654.0 cr unu---uuuuu 170330e19970401xx s 000 0 eng 10.1023/A:1012070726480 doi (NATIONALLICENCE)springer-10.1023/A:1012070726480 Sequence Alignments of the H+-Dependent Oligopeptide Transporter Family PTR: Inferences on Structure and Function of the Intestinal PET1 Transporter [Elektronische Daten] [Richard Graul, Wolfgang Sadée] Purpose. To study the structure and function of the intestinal H+/ peptide transporter PET1, we compared its amino acid sequence with those of related transporters belonging to the oligopeptide transporter family PTR, and with more distant transporter families. Methods. We have developed a new approach to the sequence analysis of proteins with multiple transmembrane domains (TMDs) which takes into account the repeated TMD-loop topology. In addition to conventional analyses of the entire sequence, each TMD and its adjacent loop residues (=TMD segments) were analyzed separately as independent structural units. In combination with hydropathy analysis, this approach reveals any changes in the order of the TMD segments in the primary structure and permits TMD alignments among divergent structures even if rearrangements of the order of TMD segments have occurred in the course of evolution. Results. Alignments of TMD segments indicate that the TMD order in PTR transporters may have changed in the process of evolution. Consideration of such changes permits the alignment of homologous TMD segments from PTR transporters belonging to distant akaryotic and eukaryotic phyla. Multiple alignments of TMDs reveal several highly conserved regions that may play a role in transporter function. In comparing the PTR transporters with other transporter gene families, alignment scores using the entire primary structure are too low to support a finding of probable homology. However, statistically significant alignments were observed among individual TMD segments if one disregards the order in which they occur in the primary structure. Conclusions. Our results support the hypothesis that the PTR transporters may have evolved by rearrangement, duplication, or insertions and deletions of TMD segments as independent modules. This modular structure suggests new alignment strategies for determining functional domains and testing relationships among distant transporter families. Plenum Publishing Corporation, 1997 PET1 nationallicence oligopeptide transporter nationallicence sequence analysis nationallicence Graul Richard Departments of Biopharmaceutical Sciences and Pharmaceutical Chemistry, University of California San Francisco, 94143-0446, San Francisco, California aut Sadée Wolfgang Departments of Biopharmaceutical Sciences and Pharmaceutical Chemistry, University of California San Francisco, 94143-0446, San Francisco, California aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/4(1997-04-01), 388-400 0724-8741 14:4<388 1997 14 11095 https://doi.org/10.1023/A:1012070726480 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012070726480 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Graul Richard Departments of Biopharmaceutical Sciences and Pharmaceutical Chemistry, University of California San Francisco, 94143-0446, San Francisco, California aut NATIONALLICENCE 700 1- Sadée Wolfgang Departments of Biopharmaceutical Sciences and Pharmaceutical Chemistry, University of California San Francisco, 94143-0446, San Francisco, California aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/4(1997-04-01), 388-400 0724-8741 14:4<388 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer