Main-chain dominated amyloid structures demonstrated by the effect of high pressure.
It has been suggested that, while the globular native forms of proteins are a side-chain-dominated compact structure evolved by pursuing a unique fold with optimal packing of amino acid residues, amyloid fibrils are a main-chain-dominated structure with an extensive hydrogen bond network. To address this issue, the effects of hydrostatic pressure on amyloid fibrils of beta2-microglobulin (beta2-m), involved in dialysis-related amyloidosis, were studied. A systematic analysis at various pressures and concentrations of guanidine hydrochloride conducted by monitoring thioflavin T fluorescence, light-scattering, and tryptophan fluorescence revealed contrasting conformational changes occurring consecutively: first, a pressure-induced reorganization of fibrils and then a pressure-induced unfolding. The changes in volume as well as the observed structural changes indicate that the beta2-m amyloid fibrils under ambient pressure are less tightly packed with a larger number of cavities, consistent with the main-chain-dominated amyloid structure. Moreover, the amyloid structure without optimal packing will enable various isoforms to form, suggesting the structural basis of multiple forms of amyloid fibrils in contrast to the unique native-fold.
Chatani
Eri
E
Institute for Protein Research, Osaka University and CREST, Japan Science and Technology Agency, Suita, Osaka 565-0871, Japan.
Kato
Michiko
M
Kawai
Tomoji
T
Naiki
Hironobu
H
Goto
Yuji
Y
D000682:Amyloid / Q000737:chemistry*; D052160:Benzothiazoles; D003956:Dialysis; D019791:Guanidine / Q000737:chemistry; D006801:Humans; D006874:Hydrostatic Pressure; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D013844:Thiazoles / Q000737:chemistry; D014364:Tryptophan / Q000737:chemistry; D001613:beta 2-Microglobulin / Q000737:chemistry*
D000682:Amyloid; D052160:Benzothiazoles; D013844:Thiazoles; D001613:beta 2-Microglobulin; C009462:thioflavin T; D014364:Tryptophan; D019791:Guanidine