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Related Concept Videos

Secondary Active Transport01:55

Secondary Active Transport

122.0K
One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme “pump” embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
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Primary Active Transport01:29

Primary Active Transport

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In contrast to passive transport, active transport involves a substance being moved through membranes in a direction against its concentration or electrochemical gradient. There are two types of active transport: primary active transport and secondary active transport. Primary active transport utilizes chemical energy from ATP to drive protein pumps embedded in the cell membrane. With energy from ATP, the pumps transport ions against their electrochemical gradients—a direction they would...
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Membrane Transporters01:31

Membrane Transporters

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Transporters are essential membrane transport proteins with functions related to cell nutrition, homeostasis, communication, etc. Approximately 7% of all genes in the human genome code for transporters or transporter-related proteins.
Transporters are mainly composed of alpha-helices, built from bundles of ten or more helices traversing the plasma membrane. The solute-binding sites are located midway, where some of the helices are broken or distorted, making space for the binding site through...
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Cotranslational Protein Translocation01:20

Cotranslational Protein Translocation

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Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
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Protein Translocation Machinery on the ER Membrane01:28

Protein Translocation Machinery on the ER Membrane

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The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
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Facilitated Diffusion01:16

Facilitated Diffusion

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The plasma membrane, a critical structure in cellular biology, houses an array of transporters, or carrier proteins, interspersed within its lipid bilayer. These proteins play a crucial role in solute transport through facilitated diffusion, a form of passive diffusion that uses transporters to move the molecules across the membrane.
In this process, substrates such as organic compounds and ions interact with a transporter on one side, triggering conformational changes in proteins that enable...
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Updated: Aug 4, 2025

A Proteoliposome-Based Efflux Assay to Determine Single-molecule Properties of Cl- Channels and Transporters
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Structure-function relationships in the sodium chloride cotransporter.

Erika Moreno1, Diana Pacheco-Alvarez2, María Chávez-Canales3

  • 1Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

Frontiers in Physiology
|March 31, 2023
PubMed
Summary

The thiazide-sensitive sodium-chloride cotransporter (NCC) is crucial for blood pressure regulation. Recent cryo-EM structures reveal its molecular details, aiding in understanding its function and drug interactions.

Keywords:
NCCphysiologysodium transportstructure-functionthiazide

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • The thiazide-sensitive sodium-chloride cotransporter (NCC) is vital for salt reabsorption in the kidney's distal convoluted tubule, playing a key role in blood pressure homeostasis.
  • NCC is the molecular target of thiazide diuretics, widely used to treat hypertension and edema.
  • NCC belongs to the electroneutral cation-coupled chloride cotransporter family and was first cloned from winter flounder.

Purpose of the Study:

  • To review the structure-function relationship of NCC, from early biochemical studies to recent structural insights.
  • To provide an overview of NCC's structural and functional aspects, highlighting key findings from various research methodologies.

Main Methods:

  • Literature review of biochemical, functional, and mutational studies on NCC.
  • Analysis of single-particle cryogenic electron microscopy (cryo-EM) data for NCC and related SLC12 family members.

Main Results:

  • Extensive studies have elucidated NCC's transmembrane domain (TM) involvement in ion and thiazide binding.
  • Functional studies identified key residues for NCC phosphorylation and glycosylation, particularly in the N-terminal domain and extracellular loop 7-8 (EL7-8).
  • High-resolution cryo-EM structures reveal an inverted conformation of TM regions and highlight two critical glycosylation sites (N-406, N-426) in EL7-8 essential for expression and function.

Conclusions:

  • Cryo-EM has provided unprecedented atomic-level structural details of NCC.
  • Understanding NCC's structure-function relationship is crucial for developing effective antihypertensive and diuretic therapies.