Early stages of beta2-microglobulin aggregation and the inhibiting action of alphaB-crystallin.
Static and dynamic light scattering experiments on extremely clean (nanofiltered) samples of the well-known amyloidogenic protein beta2-microglobulin (R3Abeta2m and WTbeta2m) evidence the self-assembly of early aggregates showing unexpected features. Further, we find that alphaB-crystallin effectively inhibits aggregation of beta2m in a far less than stoichiometric proportion, from 1:60 alphaB-crystallin monomer to beta2m monomer ratio, down to at least a 1:2 x 10(3) alphaB-crystallin oligomerto beta2m monomer ratio. Therefore, inhibition of the early stage of beta2m aggregation by alphaB-crystallin does not necessarily require a mechanicistic chaperon-like action implying one-to-one binding. This highlights the role of the free energy landscape of the system and of related modifications of solute-solvent thermodynamics caused by co-solutes, in agreement with recent work from our and other laboratories.
Department of Physical and Astronomical Sciences, University of Palermo, 36, I-90123 Palermo, Italy.
Filippo
F
Pullara
Antonio
A
Emanuele
D006801:Humans; D008027:Light; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D012542:Scattering, Radiation; D012984:Software; D013997:Time Factors; D038203:alpha-Crystallin B Chain / Q000737:chemistry*; D001613:beta 2-Microglobulin / Q000737:chemistry*
D038203:alpha-Crystallin B Chain; D001613:beta 2-Microglobulin