Differences in the molecular structure of beta(2)-microglobulin between two morphologically different amyloid fibrils.
Differences in the molecular structures of beta(2)-microglobulin between the two morphologically different amyloid fibrils having a needlelike [long-straight (LS)] and flexible [wormlike (WL)] character were investigated by infrared, Raman, and vacuum-ultraviolet circular dichroism spectroscopy. It turned out that although the beta-sheet content was comparable between the two kinds of fibrils (53 +/- 6% for the LS fibril and 47 +/- 6% for the WL fibril), the protonation states of the carboxyl side chains were distinctly different; the deprotonated (COO(-)) and protonated (COOH) forms were dominant in the LS and WL fibrils at pH 2.5, respectively, meaning that the pK(a) is specifically lowered in the LS fibril. Such a difference was not observed for the fibrils of the core fragments. Since site-specific interactions generally cause variation in the pK(a) of carboxyl side chains in proteins, these results suggest that "hook"-like interactions generated by hydrogen bonding and the formation of a salt bridge are present in the LS fibril, providing enthalpic stabilization. Presumably, the carboxyl groups fix the spatial arrangement of beta-strands and beta-sheets, bringing about the needlelike morphology. The absence of this regulation would result in the flexible morphology of the WL fibril, providing entropic stabilization.
Hiramatsu
Hirotsugu
H
Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.
Lu
Ming
M
Matsuo
Koichi
K
Gekko
Kunihiko
K
Goto
Yuji
Y
Kitagawa
Teizo
T
D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D002942:Circular Dichroism; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010843:Pichia / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D001613:beta 2-Microglobulin / Q000737:chemistry* / Q000378:metabolism
D000682:Amyloid; D005656:Fungal Proteins; D001613:beta 2-Microglobulin