The structural biology of protein aggregation diseases: Fundamental questions and some answers.
Amyloid fibrils are found in association with at least two dozen fatal diseases. The tendency of numerous proteins to convert into amyloid-like fibrils poses fundamental questions for structural biology and for protein science in general. Among these are the following: What is the structure of the cross-beta spine, common to amyloid-like fibrils? Is there a sequence signature for proteins that form amyloid-like fibrils? What is the nature of the structural conversion from native to amyloid states, and do fibril-forming proteins have two distinct stable states, the native state and the amyloid state? What is the basis of protein complementarity, in which a protein chain can bind to itself? We offer tentative answers here, based on our own recent structural studies.
Eisenberg
David
D
Howard Hughes Medical Institute, UCLA-DOE Institute of Genomics and Proteomics, Los Angeles, California 90095-1570, USA. david@mbi.ucla.edu
Nelson
Rebecca
R
Sawaya
Michael R
MR
Balbirnie
Melinda
M
Sambashivan
Shilpa
S
Ivanova
Magdalena I
MI
Madsen
Anders Ø
AØ
Riekel
Christian
C
D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
D000682:Amyloid; D011506:Proteins