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Related Concept Videos

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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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Plasma membranes have integral transmembrane proteins involved in facilitated transport. These proteins are collectively referred to as transport proteins, and they function as either channels for the material or as carriers themselves. Channel proteins have hydrophilic domains exposed to the intracellular and extracellular fluids and a hydrophilic channel through their core that provides a hydrated opening for solutes to pass through the membrane layers. Passage through the channel allows...
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Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
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Complex carbohydrates consumed cannot be absorbed into the small intestine in their original form. First, they must be hydrolyzed to a monosaccharide form such as glucose or galactose. These monosaccharides are then transported across the intestinal membrane and into the blood via transcellular transport. The intestinal epithelial cells allow the movement of these monosaccharides with a defined 'entry' through membrane transporter proteins present on their apical membrane and...
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The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
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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.
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Evolutionary balance between foldability and functionality of a glucose transporter.

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The folding pathway of human glucose transporter 3 (GLUT3) was elucidated using single-molecule magnetic tweezers. Specific lipids and endoplasmic reticulum proteins aid GLUT3

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Area of Science:

  • Structural Biology
  • Biophysics
  • Membrane Protein Folding

Background:

  • Understanding multi-pass membrane protein folding is crucial yet challenging.
  • Human glucose transporter 3 (GLUT3) is vital for glucose transport.
  • Native folding pathways of membrane proteins remain largely unknown.

Purpose of the Study:

  • To determine the folding pathway of purified human glucose transporter 3 (GLUT3).
  • To investigate the role of lipid bilayers and cellular machinery in GLUT3 folding.
  • To identify factors influencing the assembly of GLUT3's N- and C-terminal domains.

Main Methods:

  • Single-molecule magnetic tweezers to study purified GLUT3 reconstituted in synthetic lipid bilayers.
  • Analysis of folding challenges posed by polar residues in the glucose conduit.
  • Investigating the influence of endoplasmic reticulum membrane protein complex and specific lipids.

Main Results:

  • The N-terminal major facilitator superfamily (MFS) fold forms first, acting as a template.
  • Polar residues in the glucose conduit present significant folding hurdles.
  • Endoplasmic reticulum proteins assist in hydrophilic transmembrane helix insertion, promoting folding.
  • Specific lipids facilitate the final domain assembly by reducing desolvation penalties.
  • Asymmetric folding propensity is conserved in metazoan sugar porters.

Conclusions:

  • GLUT3 folding is an asymmetric process initiated by the N-terminal MFS domain.
  • Lipid-protein interactions and cellular factors are critical for proper GLUT3 assembly.
  • Evolutionary pressures create conflicts between foldability and functionality in membrane proteins.