biology

Nicotinamide ribonucleoside uptake transporters

Nicotinamide ribonucleoside uptake transporters is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Nicotinamide ribonucleoside uptake transporters rather than just read about it. In short: The Nicotinamide Ribonucleoside (NR) Uptake Permease (PnuC) Family (TC# 4.B.1) is a family of transmembrane transporters that is part of the TOG superfamily. Close PnuC homologues are found in a wide range of Gram-negative and Gram-positive bacteria, archaea and eukaryotes.

Key takeaways

Nicotinamide ribonucleoside uptake transporters belongs to biology; place it in that map before memorising details.
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Connect Nicotinamide ribonucleoside uptake transporters to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Nicotinamide ribonucleoside uptake transporters from memory before moving on to harder problems.

Reference excerpt

The Nicotinamide Ribonucleoside (NR) Uptake Permease (PnuC) Family (TC# 4.B.1) is a family of transmembrane transporters that is part of the TOG superfamily. Close PnuC homologues are found in a wide range of Gram-negative and Gram-positive bacteria, archaea and eukaryotes.

Function PnuC of Salmonella typhimurium and Haemophilus influenzae are believed to function cooperatively with NadR homologues, multifunctional proteins that together with PnuC, participate in NR phosphorylation, transport and transcriptional regulation. NadR, a cytoplasmic protein that is partly membrane associated, contains one well conserved and one poorly conserved mononucleotide-binding consensus sequence (G-X4 GKS). It drives transport and may render transport responsive to internal pyridine nucleotide levels. While its N-terminal half functions as a repressor, its C-terminal half functions as an NR kinase in a putative group translocation process.

PnuC of Haemophilus influenzae The H. influenzae homologue has been shown to transport NR from the periplasm into the cytoplasm. Phosphorylation of NR by NadR is required for NR uptake. The ribonucleoside kinase (RNK) domain has both Walker A and Walker B motifs, responsible for ATP binding and phosphoryl transfer. In addition, a proposed LID domain was identified in RNK. LID domains have been found in other kinases, and these domains are regions which are able to move after substrate binding. They are responsible for coordination of three distinct conformations, an open state in the absence of substrate, a partially closed state after substrate binding, and a fully closed state when both substrates are present. In H. influenzae, NR enters the NAD+ resynthesis pathway after phosphorylation to NMN, and subsequently, NAD+ is synthesized from NMN and ATP via an NMN adenylyl transferase activity. NadR represents a multifunctional regulator/enzyme complex able to integrate several functions, such as enzymatic catalysis, transport, and transcriptional regulatory activities.

Other constituents required for uptake The components of the H. influenzae pathway necessary for NAD+, NMN, and NR uptake have been determined. Merdanovic et al. characterized two enzymes, an outer membrane nucleotide phosphatase, and an NAD+ nucleotidase (NadN) located in the periplasm. They showed that NAD+ and NMN cross the outer membrane mainly via the OmpP2 porin. Only NR can be utilized by the PnuC transport system located in the inner membrane. The pnuC gene product is the protein that is responsible for the main flow of the NR substrate into the cytoplasm. The study of Merdanovic et al. suggests that the RNK activity of NadR determines NR transport and is negatively regulated by cytoplasmic NAD+ feedback inhibition. Therefore, NR uptake is under NadR feedback control. ATP, not the proton motive force, appears to be required for NR uptake. Thus, the driving force for NR uptake via PnuC is NR phosphorylation by NadR. A concerted group translocation mechanism can be considered whereby NadR facilitates the dissociation of NR from PnuC by phosphorylating it to NMN, thus preventing efflux of NR.

Transport reaction The proposed transport reaction catalyzed by PnuC and NadR is: NR (out) + ATP (in) → NMN (in) + ADP (in).

Structure PnuC of Salmonella typhimurium and Haemophilus influenzae are integral membrane proteins, 239 and 226 amino acyl residues (aas) in length, respectively, with 7 putative transmembrane α-helical segments. The structure of NadR has been determined. Mutations in the nadR gene which interfere with NR uptake occur in the C-terminal part of NadR. A helix-turn-helix DNA binding domain present in NadR of S. enterica serovar Typhimurium could not be found in the NadR homologue of H. influenzae. Therefore, it was proposed that in H. influenzae NadR has no regulatory function at the transcriptional level. The structures of the human NR kinase 1 (2QL6_P) with nucleotide and nucleoside substrates bound have been solved. It is structurally similar to Rossmann fold metabolite kinases. PnuC has been shown to resemble SWEET porters in overall fold, supporting the conclusion that these two families are members of the TOG superfamily.

Crystal structures NadR Protein from H. influenzae PDB: 1LW7 NR transporter PnuC PDB: 4QTN

References

Worked examples

Example 1 — a first encounter with Nicotinamide ribonucleoside uptake transporters

Start with the simplest possible case. Write down what Nicotinamide ribonucleoside uptake transporters claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Nicotinamide ribonucleoside uptake transporters before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Nicotinamide ribonucleoside uptake transporters ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Nicotinamide ribonucleoside uptake transporters

In research: Nicotinamide ribonucleoside uptake transporters appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Nicotinamide ribonucleoside uptake transporters in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Nicotinamide ribonucleoside uptake transporters is common in secondary-school and first-year university syllabi. It links to neighbouring topics Integral membrane proteins, Membrane proteins, Protein families, so understanding it makes those chapters shorter.
In everyday life: Look for Nicotinamide ribonucleoside uptake transporters outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Nicotinamide ribonucleoside uptake transporters in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Nicotinamide ribonucleoside uptake transporters means in your own words.
Compare your version with the excerpt and mark what you missed.
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Frequently asked questions

What is Nicotinamide ribonucleoside uptake transporters in simple terms?

Why does Nicotinamide ribonucleoside uptake transporters matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Nicotinamide ribonucleoside uptake transporters?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Nicotinamide ribonucleoside uptake transporters.