A Faulty Interaction Between SOD1 and HCCS in Neurodegenerative Disease

Overview

Journal Sci Rep

Specialty Science

Date 2016 Jun 11

PMID 27282955

Citations 23

Authors

Gareth S A Wright

Svetlana V Antonyuk

S Samar Hasnain

Affiliations

Soon will be listed here.

Abstract

A proportion of Amyotrophic lateral sclerosis (ALS) cases result from impaired mutant superoxide dismutase-1 (SOD1) maturation. The copper chaperone for SOD1 (hCCS) forms a transient complex with SOD1 and catalyses the final stages of its maturation. We find that a neurodegenerative disease-associated hCCS mutation abrogates the interaction with SOD1 by inhibiting hCCS zinc binding. Analogously, SOD1 zinc loss has a detrimental effect on the formation, structure and disassociation of the hCCS-SOD1 heterodimer. This suggests that hCCS functionality is impaired by ALS mutations that reduce SOD1 zinc affinity. Furthermore, stabilization of wild-type SOD1 by chemical modification including cisplatination, inhibits complex formation. We hypothesize that drug molecules designed to stabilize ALS SOD1 mutants that also target the wild-type form will lead to characteristics common in SOD1 knock-outs. Our work demonstrates the applicability of chromatographic SAXS when studying biomolecules predisposed to aggregation or dissociation; attributes frequently reported for complexes involved in neurodegenerative disease.

Citing Articles

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