Seeding-dependent propagation and maturation of beta2-microglobulin amyloid fibrils under high pressure.
High hydrostatic pressure reversibly transforms the amyloid fibrils of beta2-microglobulin (beta2-m) into a more tightly packed, reorganized structure, which has provided insight into the polymorphic properties of amyloid fibrils. Here, to further investigate the molecular mechanism that controls fibril structure, seed-dependent fibril growth from an acid-unfolded monomeric form under high pressure was studied. At all pressures up to 400 MPa, the fibril growth could be approximated by a single-exponential kinetics, although pressure above 300 MPa decreased the growth rate significantly. The fibrils formed at high pressure were similar to the reorganized fibrils formed initially at ambient pressure and then pressurized, suggesting that the reorganized fibrils were formed directly at high pressure. A systematic investigation of the extension rate under various pressures indicated that the activation free energies for the original and reorganized fibrils are significantly different, suggesting that different amino acid contacts are involved in these two types of fibrils. On the other hand, for the seed-dependent extension reactions of both types of fibrils, the activation volume was much smaller than the change in reaction volume, implying that only small numbers of side-chain interactions are achieved in the transition state. Importantly, we observed a marked acceleration of fibril growth, i.e., maturation, on repeated self-seeding above 300 MPa, revealing the coexistence of another type of fibril with a similar structure but with an increased growth-rate under high pressure.
Chatani
Eri
E
Institute for Protein Research, Osaka University and CREST, Japan Science and Technology Agency, Suita, Osaka 565-0871, Japan.
Naiki
Hironobu
H
Goto
Yuji
Y
D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D011312:Pressure; D001613:beta 2-Microglobulin / Q000737:chemistry* / Q000378:metabolism*
D000682:Amyloid; D001613:beta 2-Microglobulin