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Early stages of β2‐microglobulin aggregation and the inhibiting action of αB‐crystallin
Author(s) -
Pullara Filippo,
Emanuele Antonio
Publication year - 2008
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22122
Subject(s) - beta 2 microglobulin , crystallin , action (physics) , chemistry , protein aggregation , biophysics , biochemistry , biology , medicine , physics , quantum mechanics
Static and dynamic light scattering experiments on extremely clean (nanofiltered) samples of the well‐known amyloidogenic protein β2‐microglobulin (R3Aβ2m and WTβ2m) evidence the self‐assembly of early aggregates showing unexpected features. Further, we find that αB‐crystallin effectively inhibits aggregation of β2m in a far less than stoichiometric proportion, from 1:60 αB‐crystallin monomer to β2m monomer ratio, down to at least a 1:2 × 10 3 αB‐crystallin oligomerto β2m monomer ratio. Therefore, inhibition of the early stage of β2m aggregation by αB‐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. Proteins 2008. © 2008 Wiley‐Liss, Inc.