Related Experiment Video

Updated: Apr 24, 2026

Assay Development for High Content Quantification of Sod1 Mutant Protein Aggregate Formation in Living Cells
11:12

Assay Development for High Content Quantification of Sod1 Mutant Protein Aggregate Formation in Living Cells

Published on: October 4, 2017

6.6K

Lipid-associated aggregate formation of superoxide dismutase-1 is initiated by membrane-targeting loops

Choon-Peng Chng1, Richard W Strange

  • 1Biophysical Modeling Group, Bioinformatics Institute, A*STAR (Agency for Science, Technology and Research), Singapore, 138671, Republic of Singapore.

Proteins
|September 13, 2014
PubMed

Insights

Apo-SOD1 monomers bind to cell membranes via flexible loops, not hydrophobic interfaces. This interaction is crucial for copper uptake and may initiate SOD1 aggregation linked to neurodegenerative diseases.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Neuroscience

Background:

  • Copper-Zinc superoxide dismutase 1 (SOD1) protects cells from oxidative stress.
  • Misfolded or demetallated SOD1 is implicated in amyotrophic lateral sclerosis (ALS) pathogenesis.
  • The interaction of apo-SOD1 with cell membranes is poorly understood.

Purpose of the Study:

  • To elucidate the mechanism by which apo-SOD1 interacts with phospholipid bilayers.
  • To investigate the role of specific apo-SOD1 structural elements in lipid binding.
  • To understand how apo-SOD1 membrane association may contribute to disease.

Main Methods:

  • Atomistic molecular dynamics simulations were employed.
  • The binding of apo-SOD1 dimers and monomers to phospholipid bilayers was analyzed.
  • Protein-lipid interactions and conformational changes were examined.

Main Results:

  • Flexible electrostatic and zinc-binding loops in apo-SOD1 facilitate binding to lipids without significant unfolding.
  • Apo-SOD1 monomers associate with the bilayer primarily through the zinc-binding loop.
  • The observed monomer orientation supports copper chaperone interaction and potential aggregation seeding.

Conclusions:

  • Flexible loops are key for apo-SOD1 membrane association.
  • This interaction mechanism is vital for copper ion acquisition and SOD1 aggregation in neurodegeneration.
  • Findings provide insights into the early stages of SOD1-related cellular dysfunction.
Keywords:
1-octanolamyotrophic lateral sclerosismembrane-targeting loopsmotor neuron diseaseprotein-lipid co-aggregation

More Related Videos

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils15:04

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils

Published on: September 28, 2019

5.3K
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

8.2K

Related Concept Videos

The Supercomplexes in the Crista Membrane01:41

The Supercomplexes in the Crista Membrane

The mitochondrial cristae membrane is the primary site for the oxidative phosphorylation (OXPHOS) process of energy conversion mediated through respiratory complexes I to V. These complexes have been widely studied for decades, and it has been proven that they form supramolecular structures called respiratory supercomplexes (SC). These higher-order complexes may be crucial in maintaining the biochemical structure and improving the physiological activity of the individual complexes while...
2.2K
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...
3.2K
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,...
10.1K
Protein Modifications in the RER01:26

Protein Modifications in the RER

Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
5.6K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
8.8K
Formation of Lipopolysaccharides01:19

Formation of Lipopolysaccharides

Lipopolysaccharides (LPS) are crucial components of the outer membrane of Gram-negative bacteria, serving both structural and functional roles. It contributes to membrane stability and protects bacteria from host immune responses. LPS is composed of three major regions—lipid A, a core oligosaccharide, and an O antigen. The biosynthesis and assembly of LPS involve a highly coordinated set of enzymatic reactions and transport mechanisms. Additionally, LPS is recognized as an endotoxin,...
1.1K