Differences in the molecular structure of β2-microglobulin between two morphologically different amyloid fibrils

Hirotsugu Hiramatsu, Ming Lu, Koichi Matsuo, Kunihiko Gekko, Yuji Goto, Teizo Kitagawa

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Differences in the molecular structures of β2-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 β-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 pKa is specifically lowered in the LS fibril. Such a differencewas not observed for the fibrils of the core fragments. Since site-specific interactions generally cause variation in the pKa 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 β-strands and β-sheets, bringing about the needlelike morphology. The absence of this regulationwould result in the flexiblemorphology of the WL fibril, providing entropic stabilization.

Original languageEnglish
Pages (from-to)742-751
Number of pages10
JournalBiochemistry
Volume49
Issue number4
DOIs
Publication statusPublished - 2010 Feb 2

ASJC Scopus subject areas

  • Biochemistry

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