Structural insights into substrate recognition in proton‐dependent oligopeptide transporters

Guettou, Fatma; Quistgaard, E.M.; Tresaugues, L.; Moberg, Per; Jegerschöld, Caroline; Zhu, Lin; Jong, Agnes; Nordlund, P.; Löw, Christian

doi:10.1038/embor.2013.107

Cited by 95 publications

(127 citation statements)

References 27 publications

Supporting

Mentioning

118

Contrasting

Order By: Relevance

“…Arrangement and orientation of helix-triplets in PepT. The oligopeptide/ H + symporter (PepT) (19,30,31,35) provides another variation to the order of the triple-helix units because the symmetry motifs Table 1). Clearly, the orientations of motifs A and D are inverted with respect to the membrane relative to LacY (Figs.…”

Section: An Overall Mechanism For Coupling In Lacymentioning

confidence: 99%

Evolutionary mix-and-match with MFS transporters II

Madej

Kaback

2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

One fundamentally important problem for understanding the mechanism of coupling between substrate and H + translocation with secondary active transport proteins is the identification and physical localization of residues involved in substrate and H + binding. This information is exceptionally difficult to obtain with the Major Facilitator Superfamily (MFS) because of the broad sequence diversity of the members. The MFS is the largest and most diverse group of transporters, many of which are clinically important, and includes members from all kingdoms of life. A wide range of substrates is transported, in many instances against a concentration gradient by transduction of the energy stored in an H + electrochemical gradient using symport mechanisms, which are discussed herein. Crystallographic structures of MFS members indicate that a deep central hydrophilic cavity surrounded by 12 mostly irregular transmembrane helices represents a common structural feature. An inverted triple-helix structural symmetry motif within the N-and C-terminal six-helix bundles suggests that the proteins may have arisen by intragenic multiplication. In the work presented here, the triple-helix motifs are aligned in combinatorial fashion so as to detect functionally homologous positions with known atomic structures of MFS members. Substrate and H + -binding sites in symporters that transport substrates, ranging from simple ions like phosphate to more complex peptides or disaccharides, are found to be in similar locations. It also appears likely that there is a homologous ordered kinetic mechanism for the H + -coupled MFS symporters.membrane transport | sequence alignment | bioenergetics

show abstract

Section: An Overall Mechanism For Coupling In Lacymentioning

confidence: 99%

Evolutionary mix-and-match with MFS transporters II

Madej

Kaback

2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Collectively, these observations show that the C-terminal side-chain-binding site on NmPOT is not adapted to accommodating a positively charged side chain. A number of bacterial POTs have been overexpressed recombinantly in the past and subsequently characterized functionally [Doki et al, 2013;Ernst et al, 2009;Guettou et al, 2013;Jensen et al, 2012a;Weitz et al, 2007]. Based mostly on competition studies, the consensus is that diand tripeptides are recognized with similar affinities and mono-and tetrapeptides are poor competitors, although some POTs do show a preference for dipeptides rather than tripeptides [Ernst et al, 2009].…”

Section: Resultsmentioning

confidence: 99%

Peptide Selectivity of the Proton-Coupled Oligopeptide Transporter from <b><i>Neisseria meningitidis</i></b>

Sharma¹,

Aduri²,

Iqbal³

et al. 2016

Microb Physiol

View full text Add to dashboard Cite

Peptide transport in living organisms is facilitated by either primary transport, hydrolysis of ATP, or secondary transport, cotransport of protons. In this study, we focused on investigating the ligand specificity of the Neisseria meningitidis proton-coupled oligopeptide transporter (NmPOT). It has been shown that the gene encoding this transporter is upregulated during infection. NmPOT conformed to the typical chain length preference as observed in prototypical transporters of this family. In contrast to prototypical transporters, it was unable to accommodate a positively charged peptide residue at the C-terminus position of the substrate peptide. Sequence analysis of the active site of NmPOT displayed a distinctive aromatic patch, which has not been observed in any other transporters from this family. This aromatic patch may be involved in providing NmPOT with its atypical preferences. This study provides important novel information towards understanding how these transporters recognize their substrates.

show abstract

“…In PepT St and GkPOT this interaction is made by an arginine on H1 and a conserved glutamate on H7, whereas in PepT So , and very likely the mammalian PepT1 and PepT2 transporters, the interaction is through a conserved histidine on H2 to an aspartate on H7 [30]. Interestingly, this interaction is absent in PepT So2 , a related transporter from S. oniedensis [33] and also NRT1.1, showing that this region of the transporter is able to change. A further site of proton binding was also discovered in the POT family, residing in the ExxER motif on H1, with a key role in transport [18].…”

Section: Salt Bridge Network and Proton Bindingmentioning

confidence: 95%

Symmetry and Structure in the POT Family of Proton Coupled Peptide Transporters

Newstead

2017

Symmetry

View full text Add to dashboard Cite

Abstract:The POT family of proton coupled oligopeptide transporters belong to the Major Facilitator Superfamily of secondary active transporters and are found widely distributed in bacterial, plant, fungal and animal genomes. POT transporters use the inwardly directed proton electrochemical gradient to drive the concentrative uptake of di-and tri-peptides across the cell membrane for metabolic assimilation. Mammalian members of the family, PepT1 and PepT2, are responsible for the uptake and retention of dietary protein in the human body, and due to their promiscuity in ligand recognition, play important roles in the pharmacokinetics of drug transport. Recent crystal structures of bacterial and plant members have revealed the overall architecture for this protein family and provided a framework for understanding proton coupled transport within the POT family. An interesting outcome from these studies has been the discovery of symmetrically equivalent structural and functional sites. This review will highlight both the symmetry and asymmetry in structure and function within the POT family and discuss the implications of these considerations in understanding transport and regulation.

show abstract

Structural insights into substrate recognition in proton‐dependent oligopeptide transporters

Cited by 95 publications

References 27 publications

Evolutionary mix-and-match with MFS transporters II

Evolutionary mix-and-match with MFS transporters II

Peptide Selectivity of the Proton-Coupled Oligopeptide Transporter from <b><i>Neisseria meningitidis</i></b>

Symmetry and Structure in the POT Family of Proton Coupled Peptide Transporters

Contact Info

Product

Resources

About