Related Experiment Video

Updated: May 16, 2026

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
06:45

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay

Published on: May 26, 2011

Altering hydrophobic sequence lengths shows that hydrophobic mismatch controls affinity for ordered lipid domains

Qingqing Lin1, Erwin London

  • 1Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York 11794-5215, USA.

The Journal of Biological Chemistry
|November 15, 2012
PubMed

Insights

Transmembrane protein length mismatch with lipid bilayer width influences protein affinity for membrane rafts. This finding is crucial for understanding how multi-transmembrane segment proteins assemble in rafts.

Area of Science:

  • Biochemistry
  • Membrane Biology
  • Protein-Lipid Interactions

Background:

  • Transmembrane (TM) proteins are crucial for cellular functions.
  • Lipid rafts are specialized membrane domains that compartmentalize cellular processes.
  • The interaction between TM proteins and lipid rafts is vital for protein function and assembly.

Purpose of the Study:

  • To investigate the hypothesis that the mismatch between transmembrane (TM) length and lipid bilayer width controls TM protein affinity for ordered lipid domains (rafts).
  • To elucidate the role of TM segment length in the membrane insertion and pore formation of perfringolysin O (PFO).

Main Methods:

  • Utilized perfringolysin O (PFO), a pore-forming cholesterol-dependent cytolysin, and its mutants with altered TM segment lengths.
  • Employed Förster Resonance Energy Transfer (FRET) and microscopy on various vesicle compositions to assess protein-lipid domain interactions.
  • Compared PFO behavior in lipid vesicles with differing bilayer thicknesses and domain properties.

Main Results:

  • Both wild-type and mutant PFO showed cholesterol-dependent membrane insertion.
  • Maximal PFO pore formation correlated with bilayer width matching TM segment length.
  • PFO affinity for ordered lipid domains varied significantly with TM length and bilayer width, with longer TM segments preferring thicker bilayers and shorter segments preferring thinner bilayers.

Conclusions:

  • Transmembrane segment length and lipid bilayer width mismatch critically regulates TM protein affinity for lipid rafts.
  • Multi-transmembrane segment proteins, unlike single-TM proteins, exhibit limited adaptability to bilayer width variations, potentially due to their inability to tilt.
  • This width sensitivity links raft affinity to the multimeric state of proteins, influencing the assembly of TM complexes within rafts.

More Related Videos

Using Scaffold Liposomes to Reconstitute Lipid-proximal Protein-protein Interactions In Vitro08:53

Using Scaffold Liposomes to Reconstitute Lipid-proximal Protein-protein Interactions In Vitro

Published on: January 11, 2017

Method to Visualize and Analyze Membrane Interacting Proteins by Transmission Electron Microscopy10:49

Method to Visualize and Analyze Membrane Interacting Proteins by Transmission Electron Microscopy

Published on: March 5, 2017

Related Concept Videos

Membrane Fluidity01:26

Membrane Fluidity

Membrane fluidity is explained by the fluid mosaic model of the cell membrane, which describes the plasma membrane structure as a mosaic of components—including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is a relatively...
Membrane Fluidity01:23

Membrane Fluidity

Cell membranes are composed of phospholipids, proteins, and carbohydrates loosely attached to one another through chemical interactions. Molecules are generally able to move about in the plane of the membrane, giving the membrane its flexible nature called fluidity. Two other features of the membrane contribute to membrane fluidity: the chemical structure of the phospholipids and the presence of cholesterol in the membrane.
Asymmetric Lipid Bilayer01:35

Asymmetric Lipid Bilayer

Biological membranes show uneven distribution of different types of lipids in the inner and outer layers, resulting in transverse asymmetric membranes. The treatment of the erythrocyte membrane with the enzyme phospholipase confirmed the asymmetric nature of the lipid bilayer. The enzyme hydrolyzes lipids into fatty acids and hydrophilic groups. The phospholipase acts only on the outer layer of the membrane, while the inner layer remains intact. The phospholipase treatment resulted in 80%...
Membrane Asymmetry Regulating Transporters01:19

Membrane Asymmetry Regulating Transporters

Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
Fluid Mosaic Model01:19

Fluid Mosaic Model

Scientists identified the plasma membrane in the 1890s and its principal chemical components (lipids and proteins) by 1915. The model for plasma membrane structure, proposed in 1935 by Hugh Davson and James Danielli, was the first model to be widely accepted in the scientific community. The model was based on the plasma membrane's "railroad track" appearance in early electron micrographs. Davson and Danielli theorized that the plasma membrane's structure resembled a sandwich with the analogy of...
Insertion of Multi-pass Transmembrane Proteins in the RER01:29

Insertion of Multi-pass Transmembrane Proteins in the RER

The rough ER membrane synthesizes, assembles, and embeds transmembrane proteins in diverse topologies. These proteins function as transporters or channels and can remain in the ER membrane or are sent to the Golgi complex, lysosome, and cell membrane.
The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...