Related Experiment Video
Updated: Jan 14, 2026

ALS - Motor Neuron Disease: Mechanism and Development of New Therapies
Published on: July 29, 2007
Allosteric pathway connects Zn(II) loss from SOD1 to known pathogenic mechanisms
Rocío Araya-Osorio1, Moisés Dominguez2, Sebastian Thallmair3
1Departamento de Química, Facultad de Ciencias, Universidad de Tarapacá, Arica, Chile.
None:
Cu,Zn superoxide dismutase (SOD1) is one of the proteins with mutations linked to hereditary forms of the amyotrophic lateral sclerosis neurodegenerative disorder. The protein is known for its enzymatic activity, but it has been shown to also have regulatory functions, which could be related to its pathogenic potential. Seemingly unrelated to its regulatory roles, the most important hypothesis on SOD1 pathogenicity is related to misfolding of the protein, specifically centered on the region corresponding to its residues 28-38. The present work explores the structural and dynamical effect of Zn(II) removal from SOD1, which is known to influence its regulatory roles, with coarse-grained simulations of 450μs per system. In agreement with experiment, we see an increased solvent exposure of the regulatory region (residues 5-18). We also see an increased solvent exposure of the misfolding-critical 28-38 region. We unveil the mechanism and interactions connecting Zn(II) loss, and solvent exposure of both regions. The present work allows for an unified understanding of two different pathogenic mechanisms of SOD1.
Related Concept Videos
Notch Signaling Pathway
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Allosteric Proteins-ATCase
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
The Proteasome
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...

