Amyloid Protofibril is Highly Voluminous and Compressible†


By Kazuyuki Akasaka, Akihiro Nakamura, Koichi Matsuo, Hideki Tachibana, Kunihiko Gekko, Abdul Raziq Abdul Latif.


We report here results of the first direct measurement of partial volume and compressibility changes of a protein as it forms an amyloid protofibril. We use a high precision density meter and an ultrasonic velocity meter on a solution of intrinsically denatured, disulfide-deficient variant of hen lysozyme, and follow the time-dependent changes in volume and compressibility, as the protein spontaneously forms a protofibril. We have found a large increase in partial specific volume with time from 0.684 to 0.724 mLâg-1 (˘î ) 0.040 mLâg-1 corresponding to 570 mLâ(mol monomer)-1) and in partial specific adiabatic compressibility coefficient from -7.48  10-12 to +1.35  10-12 cm2âdyn-1 (˘âs ) 8.83  10-12âcm2âdyn-1) as the monomer transforms into a protofibril. The results demonstrate that the protofibril is a highly voluminous and compressible entity, disclosing a cavity-rich, fluctuating nature for the amyloid protofibril. The volume and compressibility changes occur in two phases, the faster one preceding the major development of the â-structure in the protofibril as monitored by CD.


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