Cu/Zn superoxide dismutase can form pore-like structures

Jinhyuk Chung; Hoichang Yang; Mitchel D. De Beus; Chang Y. Ryu; Kilwon Cho; Wilfredo Colón

doi:10.1016/j.bbrc.2003.11.008

Cu/Zn superoxide dismutase can form pore-like structures

Jinhyuk Chung, Hoichang Yang, Mitchel D. De Beus, Chang Y. Ryu, Kilwon Cho, Wilfredo Colón

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

Abstract

Mutations in Cu/Zn superoxide dismutase (SOD) are associated with familial amyotrophic lateral sclerosis (FALS), a neurodegenerative disease that is characterized by the selective death of motor neurons. Despite the genetic association made between the protein and the disease, the mechanism by which the mutant SOD proteins become toxic is still a mystery. Using wild-type SOD and three pathogenic mutants (A4V, G37R, and G85R), we show that the copper-induced oxidation of metal-depleted SOD causes its in vitro aggregation into pore-like structures, as determined by atomic force microscopy. Because toxic pores have been recently implicated in the pathogenic mechanism of other neurodegenerative diseases, these results raise the possibility that the aberrant self-assembly of oxidatively damaged SOD mutants into toxic oligomers or pores may have a pathological role in FALS.

Original language	English
Pages (from-to)	873-876
Number of pages	4
Journal	Biochemical and Biophysical Research Communications
Volume	312
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2003.11.008
State	Published - 26 Dec 2003
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by a NIH Grant (R01NS42915) to W.C. H.Y. and K.C. were supported by the Ministry of Science and Technology of Korea (National Research Laboratory Project) and the Ministry of Education of Korea (BK21 Program). C.R. thanks the NSF NSEC Program (NSF DMR-0117792) for the AFM support.

Keywords

Aggregation
Amyloid
Amyotrophic lateral sclerosis
Channel
FALS
Neurodegeneration
Oxidative damage
Pore
SOD

Access to Document

10.1016/j.bbrc.2003.11.008

Cite this

@article{25c8157348c74619b471e7c20cea8d00,

title = "Cu/Zn superoxide dismutase can form pore-like structures",

abstract = "Mutations in Cu/Zn superoxide dismutase (SOD) are associated with familial amyotrophic lateral sclerosis (FALS), a neurodegenerative disease that is characterized by the selective death of motor neurons. Despite the genetic association made between the protein and the disease, the mechanism by which the mutant SOD proteins become toxic is still a mystery. Using wild-type SOD and three pathogenic mutants (A4V, G37R, and G85R), we show that the copper-induced oxidation of metal-depleted SOD causes its in vitro aggregation into pore-like structures, as determined by atomic force microscopy. Because toxic pores have been recently implicated in the pathogenic mechanism of other neurodegenerative diseases, these results raise the possibility that the aberrant self-assembly of oxidatively damaged SOD mutants into toxic oligomers or pores may have a pathological role in FALS.",

keywords = "Aggregation, Amyloid, Amyotrophic lateral sclerosis, Channel, FALS, Neurodegeneration, Oxidative damage, Pore, SOD",

author = "Jinhyuk Chung and Hoichang Yang and {De Beus}, {Mitchel D.} and Ryu, {Chang Y.} and Kilwon Cho and Wilfredo Col{\'o}n",

note = "Funding Information: This work was supported by a NIH Grant (R01NS42915) to W.C. H.Y. and K.C. were supported by the Ministry of Science and Technology of Korea (National Research Laboratory Project) and the Ministry of Education of Korea (BK21 Program). C.R. thanks the NSF NSEC Program (NSF DMR-0117792) for the AFM support.",

year = "2003",

month = dec,

day = "26",

doi = "10.1016/j.bbrc.2003.11.008",

language = "English",

volume = "312",

pages = "873--876",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Elsevier B.V.",

number = "4",

}

TY - JOUR

T1 - Cu/Zn superoxide dismutase can form pore-like structures

AU - Chung, Jinhyuk

AU - Yang, Hoichang

AU - De Beus, Mitchel D.

AU - Ryu, Chang Y.

AU - Cho, Kilwon

AU - Colón, Wilfredo

N1 - Funding Information: This work was supported by a NIH Grant (R01NS42915) to W.C. H.Y. and K.C. were supported by the Ministry of Science and Technology of Korea (National Research Laboratory Project) and the Ministry of Education of Korea (BK21 Program). C.R. thanks the NSF NSEC Program (NSF DMR-0117792) for the AFM support.

PY - 2003/12/26

Y1 - 2003/12/26

N2 - Mutations in Cu/Zn superoxide dismutase (SOD) are associated with familial amyotrophic lateral sclerosis (FALS), a neurodegenerative disease that is characterized by the selective death of motor neurons. Despite the genetic association made between the protein and the disease, the mechanism by which the mutant SOD proteins become toxic is still a mystery. Using wild-type SOD and three pathogenic mutants (A4V, G37R, and G85R), we show that the copper-induced oxidation of metal-depleted SOD causes its in vitro aggregation into pore-like structures, as determined by atomic force microscopy. Because toxic pores have been recently implicated in the pathogenic mechanism of other neurodegenerative diseases, these results raise the possibility that the aberrant self-assembly of oxidatively damaged SOD mutants into toxic oligomers or pores may have a pathological role in FALS.

AB - Mutations in Cu/Zn superoxide dismutase (SOD) are associated with familial amyotrophic lateral sclerosis (FALS), a neurodegenerative disease that is characterized by the selective death of motor neurons. Despite the genetic association made between the protein and the disease, the mechanism by which the mutant SOD proteins become toxic is still a mystery. Using wild-type SOD and three pathogenic mutants (A4V, G37R, and G85R), we show that the copper-induced oxidation of metal-depleted SOD causes its in vitro aggregation into pore-like structures, as determined by atomic force microscopy. Because toxic pores have been recently implicated in the pathogenic mechanism of other neurodegenerative diseases, these results raise the possibility that the aberrant self-assembly of oxidatively damaged SOD mutants into toxic oligomers or pores may have a pathological role in FALS.

KW - Aggregation

KW - Amyloid

KW - Amyotrophic lateral sclerosis

KW - Channel

KW - FALS

KW - Neurodegeneration

KW - Oxidative damage

KW - Pore

KW - SOD

UR - http://www.scopus.com/inward/record.url?scp=0344495441&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2003.11.008

DO - 10.1016/j.bbrc.2003.11.008

M3 - Article

C2 - 14651952

AN - SCOPUS:0344495441

SN - 0006-291X

VL - 312

SP - 873

EP - 876

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -

Cu/Zn superoxide dismutase can form pore-like structures

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this