Atomic View of a Toxic Amyloid Small Oligomer

被引：483

作者：

Laganowsky, Arthur ^{[1
,2
]}

Liu, Cong ^{[1
,2
]}

Sawaya, Michael R. ^{[1
,2
]}

Whitelegge, Julian P. ^{[3
]}

Park, Jiyong ^{[1
,2
]}

Zhao, Minglei ^{[1
,2
]}

Pensalfini, Anna ^{[4
]}

Soriaga, Angela B. ^{[1
,2
]}

Landau, Meytal ^{[1
,2
]}

Teng, Poh K. ^{[1
,2
]}

Cascio, Duilio ^{[1
,2
]}

Glabe, Charles ^{[4
]}

Eisenberg, David ^{[1
,2
]}

机构：

[1] Univ Calif Los Angeles, Howard Hughes Med Inst, UCLA DOE Inst Genom & Prote, Dept Biol Chem, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Howard Hughes Med Inst, UCLA DOE Inst Genom & Prote, Dept Chem & Biochem, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Neuropsychiat Inst NPI, Los Angeles, CA 90024 USA

[4] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA

来源：

SCIENCE | 2012年 / 335卷 / 6073期

基金：

美国国家科学基金会;

关键词：

BETA-SHEET; GEOMETRICAL PROPERTIES; FIBRILLAR OLIGOMERS; ALZHEIMERS-DISEASE; CRYSTAL-STRUCTURES; PROTEINS; POLYPEPTIDE; MEMBRANE; FRAGMENT; PROVIDES;

D O I：

10.1126/science.1213151

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Amyloid diseases, including Alzheimer's, Parkinson's, and the prion conditions, are each associated with a particular protein in fibrillar form. These amyloid fibrils were long suspected to be the disease agents, but evidence suggests that smaller, often transient and polymorphic oligomers are the toxic entities. Here, we identify a segment of the amyloid-forming protein alpha B crystallin, which forms an oligomeric complex exhibiting properties of other amyloid oligomers: beta-sheet-rich structure, cytotoxicity, and recognition by an oligomer-specific antibody. The x-ray-derived atomic structure of the oligomer reveals a cylindrical barrel, formed from six antiparallel protein strands, that we term a cylindrin. The cylindrin structure is compatible with a sequence segment from the beta-amyloid protein of Alzheimer's disease. Cylindrins offer models for the hitherto elusive structures of amyloid oligomers.

引用

页码：1228 / 1231

页数：4

共 50 条

[1] Structural conversion of neurotoxic amyloid-β1-42 oligomers to fibrils [J].

Ahmed, Mahiuddin ;

Davis, Judianne ;

Aucoin, Darryl ;

Sato, Takeshi ;

Ahuja, Shivani ;

Aimoto, Saburo ;

Elliott, James I. ;

Van Nostrand, William E. ;

Smith, Steven O. .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2010, 17 (05) :561-U56

[2] Designing peptide inhibitors for oligomerization and toxicity of Alzheimer's β-amyloid peptide [J].

Austen, Brian M. ;

Paleologou, Katerina E. ;

Ali, Sumaya A. E. ;

Qureshi, Mohamed M. ;

Allsop, David ;

El-Agnaf, Omar M. A. .

BIOCHEMISTRY, 2008, 47 (07) :1984-1992

[3] Propagating structure of Alzheimer's β-amyloid(10-35) is parallel β-sheet with residues in exact register [J].

Benzinger, TLS ;

Gregory, DM ;

Burkoth, TS ;

Miller-Auer, H ;

Lynn, DG ;

Botto, RE ;

Meredith, SC .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (23) :13407-13412

[4]

Bernstein SL, 2009, NAT CHEM, V1, P326, DOI [10.1038/nchem.247, 10.1038/NCHEM.247]

[5] Elucidation of primary structure elements controlling early amyloid β-protein oligomerization [J].

Bitan, G ;

Vollers, SS ;

Teplow, DB .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (37) :34882-34889

[6] Neurotoxic protein oligomers - what you see is not always what you get [J].

Bitan, G ;

Fradinger, EA ;

Spring, SM ;

Teplow, DB .

AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS, 2005, 12 (02) :88-95

[7] Protofibrils, pores, fibrils, and neurodegeneration: Separating the responsible protein aggregates from the innocent bystanders [J].

Caughey, B ;

Lansbury, PT .

ANNUAL REVIEW OF NEUROSCIENCE, 2003, 26 :267-298

[8] Evidence of fibril-like β-sheet structures in a neurotoxic amyloid intermediate of Alzheimer's β-amyloid [J].

Chimon, Sandra ;

Shaibat, Medhat A. ;

Jones, Christopher R. ;

Calero, Diana C. ;

Aizezi, Buzulagu ;

Ishii, Yoshitaka .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2007, 14 (12) :1157-1164

[9] Protein misfolding, functional amyloid, and human disease [J].

Chiti, Fabrizio ;

Dobson, Christopher M. .

ANNUAL REVIEW OF BIOCHEMISTRY, 2006, 75 :333-366

[10] Amyloid formation by globular proteins under native conditions [J].

Chiti, Fabrizio ;

Dobson, Christopher M. .

NATURE CHEMICAL BIOLOGY, 2009, 5 (01) :15-22

← 1 2 3 4 5 →