Related Experiment Video

Updated: Nov 18, 2025

Method to Visualize and Analyze Membrane Interacting Proteins by Transmission Electron Microscopy
10:49

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

Published on: March 5, 2017

13.6K

Fuzzy Association of an Intrinsically Disordered Protein with Acidic Membranes

Alan Hicks1,1,2, Cristian A Escobar1,3, Timothy A Cross1,1,3

  • 1Institute of Molecular Biophysics, Department of Physics, and Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306, United States.

JACS Au
|February 8, 2021
PubMed

Insights

Disordered protein regions in Mycobacterium tuberculosis (Mtb) interact dynamically with cell membranes. Arginine residues drive these fuzzy interactions, influencing lipid positioning and protein binding specificity.

Area of Science:

  • Biophysics
  • Molecular Biology
  • Microbiology

Background:

  • Many cellular processes involve proteins interacting with lipid membranes.
  • Intrinsically disordered protein regions contribute to dynamic membrane associations.
  • Mycobacterium tuberculosis (Mtb) cell division relies on complex protein-membrane interactions.

Purpose of the Study:

  • To characterize the extreme fuzzy membrane association of the Mtb ChiZ protein's N-terminal region (NT).
  • To elucidate the role of protein dynamics and lipid composition in this interaction.
  • To investigate the molecular recognition mechanisms of disordered proteins at membranes.

Main Methods:

  • Solution and solid-state NMR spectroscopy
  • Molecular dynamics simulations
  • Biophysical characterization of protein-lipid interactions

Main Results:

  • The NT region remains disordered upon membrane association.
  • Arginine residues, particularly in the conserved second half of NT, mediate lipid interactions.
  • Lipids dynamically redistribute, with acidic lipids favoring Arg-proximal positions.
  • Asymmetric protein engagement results from competition for Arg interactions and is enhanced by a transmembrane helix.

Conclusions:

  • Fuzzy membrane association of disordered proteins is driven by specific residue interactions, not just random encounters.
  • Arginine-mediated interactions and lipid redistribution contribute to semispecific molecular recognition.
  • This mechanism may be a general strategy for disordered proteins targeting biological membranes.

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

9.2K
Reconstitution of Msp1 Extraction Activity with Fully Purified Components05:52

Reconstitution of Msp1 Extraction Activity with Fully Purified Components

Published on: August 10, 2021

2.8K

Related Concept Videos

Intrinsically Disordered Proteins02:18

Intrinsically Disordered Proteins

Intrinsically disordered proteins are a group of proteins that do not fold into specific three-dimensional structures. Their structural flexibility allows them to complement ordered proteins to perform functions that are inaccessible to rigid structures. They are more common in eukaryotes than prokaryotes and may either be exclusively intrinsically disordered or hybrid proteins, consisting of a mix of ordered and disordered regions. The absence of a rigid structure in these proteins can be...
18.8K
Intrinsically Disordered Proteins02:18

Intrinsically Disordered Proteins

2.5K
Mechanisms of Membrane Domain Formation00:59

Mechanisms of Membrane Domain Formation

Different physical properties of lipids and proteins allow them to localize and form distinct islands or domains in the membrane. Some membrane domains are formed due to protein-protein interactions, whereas others are formed due to the presence of specific lipids such as sphingolipids and sterols—for example, large proteins, such as bacteriorhodopsin, aggregate and create distinct domains.
Another mechanism for membrane domain formation involves membrane proteins interacting with...
3.5K
Membrane Proteins01:30

Membrane Proteins

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...
27.8K
Introduction to Membrane Proteins01:16

Introduction to Membrane Proteins

The cell membrane, or plasma membrane, is an ever-changing landscape. It is described as a fluid mosaic where various macromolecules are embedded in the phospholipid bilayer. Among the macromolecules are proteins. The protein content varies across cell types. For example, mitochondrial inner membranes contain ~76% protein content, while myelin contains ~18% protein content. Individual cells contain many types of membrane proteins—red blood cells contain over 50—and different cell...
77.5K
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining,...
11.1K