Crystal structure of the vitamin B3 transporter PnuC, a full-length SWEET homolog

Jaehme, Michael; Guskov, Albert; Slotboom, Dirk Jan

doi:10.1038/nsmb.2909

Cited by 37 publications

(50 citation statements)

References 27 publications

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“…LacZ-and PhoA-PnuC fusions indicate that the N-and C-termini of PnuC from H. influenzae are located in the cytoplasm and that the protein contains eight α-helical transmembrane segments (TMs) (Sauer et al, 2004). The recently solved crystal structure of PnuC from N. mucosa, a close homolog of H. influenzae PnuC (47% identity, Figure 2), confirmed this model (Jaehme et al, 2014) ( Figure 3A); however, the number of TMs is conserved neither among the PnuC homologs nor in the other Pnu transporter. The N-terminal helix is absent in many members.…”

Section: Structural Features Of Pnu Transporters Oligomeric State Of supporting

confidence: 50%

“…One of these predictions was confirmed experimentally when Pnu transporters specific for riboflavin were characterized (Vogl et al, 2007). Finally, the first crystal structure of a Pnu transporter was solved last year (Jaehme et al, 2014). The structural information provides insight into the mechanism of transport and explains many results from earlier functional studies.…”

Section: Introductionmentioning

confidence: 56%

“…The difference in the number of TMs possibly correlates with differences in the oligomeric state of Pnu transporters. PnuC from N. mucosa has eight TMs and is trimeric in detergent solution ( Figure 3B), whereas its homolog from E. coli has seven TMs and is monomeric (Jaehme et al, 2014). The crystal structure of N. mucosa PnuC shows that the non-conserved N-terminal helix is essential for interactions between the subunits in the trimer ( Figure 3B), providing a structural explanation for the monomeric state of Pnu homologs with seven TMs.…”

Section: Structural Features Of Pnu Transporters Oligomeric State Of mentioning

confidence: 97%

“…NR is one of several related compounds (vitamers) that have been named vitamin B3 and is a precursor of the cofactor NAD (Figure 1), which is found in all living organisms. The specificity of PnuC for NR has been demonstrated for homologs from Escherichia coli (Sauer et al, 2004), Haemophilus influenzae (Kemmer et al, 2001), Haemophilus parainfluenzae (Cynamon et al, 1988), S. typhimurium (Grose et al, 2005b), and Neisseria mucosa (Jaehme et al, 2014). In contrast to other Pnu homologs, the genomic organization of the genes encoding PnuC is not well conserved.…”

Section: Tracking Pnu Transporter Homologsmentioning

confidence: 98%

“…The intracellular gate consists of two layers of symmetry-related residues, which seal the central pore from the cytoplasmic side. The outer layer consists of two tryptophans provided by TM3 (Trp106) and TM7 (Trp228) ( Figure 4C) and the inner layer is formed by the symmetry-related Val57 (TM1) and Met174 (TM5), which face each other and are oriented at an angle of approximately 90° compared to the pair of tryptophans (Jaehme et al, 2014). The access pathway to the binding pocket from the periplasmic side is much more complex.…”

Section: Structural Basis Of Gating Of Pnucmentioning

confidence: 99%

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Structure, function, evolution and application of bacterial Pnu-type vitamin transporters

Jaehme

Slotboom

2015

Biological Chemistry

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Many bacteria can take up vitamins from the environment via specific transport machineries. Uptake is essential for organisms that lack complete vitamin biosynthesis pathways, but even in the presence of biosynthesis routes uptake is likely preferred, because it is energetically less costly. Pnu transporters represent a class of membrane transporters for a diverse set of B-type vitamins. They were identified 30 years ago and catalyze transport by the mechanism of facilitated diffusion, without direct coupling to ATP hydrolysis or transport of coupling ions. Instead, directionality is achieved by metabolic trapping, in which the vitamin substrate is converted into a derivative that cannot be transported, for instance by phosphorylation. The recent crystal structure of the nicotinamide riboside transporter PnuC has provided the first insights in substrate recognition and selectivity. Here, we will summarize the current knowledge about the function, structure, and evolution of Pnu transporters. Additionally, we will highlight their role for potential biotechnological and pharmaceutical applications.

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Section: Structural Features Of Pnu Transporters Oligomeric State Of supporting

confidence: 50%

Section: Introductionmentioning

confidence: 56%

Section: Structural Features Of Pnu Transporters Oligomeric State Of mentioning

confidence: 97%

Section: Tracking Pnu Transporter Homologsmentioning

confidence: 98%

Section: Structural Basis Of Gating Of Pnucmentioning

confidence: 99%

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Structure, function, evolution and application of bacterial Pnu-type vitamin transporters

Jaehme

Slotboom

2015

Biological Chemistry

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Food Fermentation: A Sustainable Approach to Enrich Water Soluble Vitamins

Rastogi,

Mishra,

Singh

2024

World Sustainability Series

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Pseudo-Symmetric Assembly of Protodomains as a Common Denominator in the Evolution of Polytopic Helical Membrane Proteins

2020

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The polytopic helical membrane proteome is dominated by proteins containing seven transmembrane helices (7TMHs). They cannot be grouped under a monolithic fold or superfold. However, a parallel structural analysis of folds around that magic number of seven in distinct protein superfamilies (SWEET, PnuC, TRIC, FocA, Aquaporin, GPCRs) reveals a common homology, not in their structural fold, but in their systematic pseudo-symmetric construction during their evolution. Our analysis leads to guiding principles of intragenic duplication and pseudo-symmetric assembly of ancestral transmembrane helical protodomains, consisting of 3 (or 4) helices. A parallel deconstruction and reconstruction of these domains provides a structural and mechanistic framework for their evolutionary paths. It highlights the conformational plasticity inherent to fold formation itself, the role of structural as well as functional constraints in shaping that fold, and the usefulness of protodomains as a tool to probe convergent vs divergent evolution. In the case of FocA vs. Aquaporin, this protodomain analysis sheds new light on their potential divergent evolution at the protodomain level followed by duplication and parallel evolution of the two folds. GPCR domains, whose function does not seem to require symmetry, nevertheless exhibit structural pseudosymmetry. Their construction follows the same protodomain assembly as any other pseudo-symmetric protein suggesting their potential evolutionary origins. Interestingly, all the 6/7/8TMH pseudo-symmetric folds in this study also assemble as oligomeric forms in the membrane, emphasizing the role of symmetry in evolution, revealing self-assembly and co-evolution not only at the protodomain level but also at the domain level.

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Crystal structure of the vitamin B3 transporter PnuC, a full-length SWEET homolog

Cited by 37 publications

References 27 publications

Structure, function, evolution and application of bacterial Pnu-type vitamin transporters

Structure, function, evolution and application of bacterial Pnu-type vitamin transporters

Food Fermentation: A Sustainable Approach to Enrich Water Soluble Vitamins

Pseudo-Symmetric Assembly of Protodomains as a Common Denominator in the Evolution of Polytopic Helical Membrane Proteins

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