Projection structure of DtpD (YbgH), a prokaryotic member of the peptide transporter family

Casagrande, Fabio; Harder, Daniel; Schenk, Andreas; Meury, Marcel; Ucurum, Zohre; Engel, Andreas; Weitz, Dietmar; Daniel, Hannelore; Fotiadis, Dimitrios (2009). Projection structure of DtpD (YbgH), a prokaryotic member of the peptide transporter family. Journal of molecular biology, 394(4), pp. 708-17. Amsterdam: Elsevier 10.1016/j.jmb.2009.09.048

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Cellular uptake of di- and tripeptides has been characterized in numerous organisms, and various transporters have been identified. In contrast, structural information on peptide transporters is very sparse. Here, we have cloned, overexpressed, purified, and biochemically characterized DtpD (YbgH) from Escherichia coli, a prokaryotic member of the peptide transporter family. Its homologues in mammals, PEPT1 (SLC15A1) and PEPT2 (SLC15A2), not only transport peptides but also are of relevance for uptake of drugs as they accept a large spectrum of peptidomimetics such as beta-lactam antibiotics, antivirals, peptidase inhibitors, and others as substrates. Uptake experiments indicated that DtpD functions as a canonical peptide transporter and is, therefore, a valid model for structural studies of this family of proteins. Blue native polyacrylamide gel electrophoresis, gel filtration, and transmission electron microscopy of single-DtpD particles suggest that the transporter exists in a monomeric form when solubilized in detergent. Two-dimensional crystallization of DtpD yielded first tubular crystals that allowed the determination of a projection structure at better than 19 A resolution. This structure of DtpD represents the first structural view of a member of the peptide transporter family.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Meury, Marcel, Fotiadis, Dimitrios José

ISSN:

0022-2836

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:12

Last Modified:

05 Dec 2022 14:22

Publisher DOI:

10.1016/j.jmb.2009.09.048

PubMed ID:

19782088

Web of Science ID:

000272602900012

URI:

https://boris.unibe.ch/id/eprint/31627 (FactScience: 196258)

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