NDLI: Folding of human superoxide dismutase: Disulfide reduction prevents dimerization and produces marginally stable monomers

Content Provider	PubMed Central
Author	Lindberg, Mikael J. Normark, Johanna Holmgren, Arne Mikael, Oliveberg
Copyright Year	2004
Abstract	The molecular mechanism by which the homodimeric enzyme Cu/Zn superoxide dismutase (SOD) causes neural damage in amytrophic lateral sclerosis is yet poorly understood. A striking, as well as an unusual, feature of SOD is that it maintains intrasubunit disulfide bonds in the reducing environment of the cytosol. Here, we investigate the role of these disulfide bonds in folding and assembly of the SOD apo protein (apoSOD) homodimer through extensive protein engineering. The results show that apoSOD folds in a simple three-state process by means of two kinetic barriers: 2D⇌2M⇌M2. The early predominant barrier represents folding of the monomers (M), and the late barrier the assembly of the dimer (M2). Unique for this mechanism is a dependence of protein concentration on the unfolding rate constant under physiological conditions, which disappears above 6 M Urea where the transition state for unfolding shifts to first-order dissociation of the dimer in accordance with Hammond-postulate behavior. Although reduction of the intrasubunit disulfide bond C57–C146 is not critical for folding of the apoSOD monomer, it has a pronounced effect on its stability and abolishes subsequent dimerization. Thus, impaired ability to form, or retain, the C57–C146 bond in vivo is predicted to increase the cellular load of marginally stable apoSOD monomers, which may have implications for the amytrophic lateral sclerosis neuropathology.
Related Links	http://dx.doi.org/10.1073/pnas.0403979101
Ending Page	15898
Page Count	6
Starting Page	15893
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	45
Volume Number	101
Language	English
Publisher	National Academy of Sciences
Publisher Date	2004-11-09
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Dynamical roles of metal ions and the disulfide bond in Cu, Zn superoxide dismutase folding and aggregation

Overexpression of human copper,zinc-superoxide dismutase (SOD1) prevents postischemic injury

A Primary Role for Disulfide Formation in the Productive Folding of Prokaryotic Cu,Zn-superoxide Dismutase

The dual nature of human extracellular superoxide dismutase: one sequence and two structures.

The Unusually Stable Quaternary Structure of Human Cu,Zn-Superoxide Dismutase 1 Is Controlled by Both Metal Occupancy and Disulfide Status

Loss of Metal Ions, Disulfide Reduction and Mutations Related to Familial ALS Promote Formation of Amyloid-Like Aggregates from Superoxide Dismutase

Chronic inhibition of superoxide dismutase produces apoptotic death of spinal neurons.

Fibrillation precursor of superoxide dismutase 1 revealed by gradual tuning of the protein-folding equilibrium

Aerosolized Human Extracellular Superoxide Dismutase Prevents Hyperoxia-Induced Lung Injury

Folding of human superoxide dismutase: Disulfide reduction prevents dimerization and produces marginally stable monomers

Similar Documents

Dynamical roles of metal ions and the disulfide bond in Cu, Zn superoxide dismutase folding and aggregation

Overexpression of human copper,zinc-superoxide dismutase (SOD1) prevents postischemic injury

A Primary Role for Disulfide Formation in the Productive Folding of Prokaryotic Cu,Zn-superoxide Dismutase

The dual nature of human extracellular superoxide dismutase: one sequence and two structures.

The Unusually Stable Quaternary Structure of Human Cu,Zn-Superoxide Dismutase 1 Is Controlled by Both Metal Occupancy and Disulfide Status

Loss of Metal Ions, Disulfide Reduction and Mutations Related to Familial ALS Promote Formation of Amyloid-Like Aggregates from Superoxide Dismutase

Chronic inhibition of superoxide dismutase produces apoptotic death of spinal neurons.

Fibrillation precursor of superoxide dismutase 1 revealed by gradual tuning of the protein-folding equilibrium

Aerosolized Human Extracellular Superoxide Dismutase Prevents Hyperoxia-Induced Lung Injury

Folding of human superoxide dismutase: Disulfide reduction prevents dimerization and produces marginally stable monomers