A Comprehensive Model for Packing and Hydration for Amyloid Fibrils of β2-Microglobulin

Volume can provide informative structural descriptions of macromolecules such as proteins in solution because a final volumetric outcome accompanies the exquisite equipoise of packing effects between residues, and residues and waters inside and outside proteins. Here we performed systematic investigations on the volumetric nature of the amyloidogenic conformations of beta(2)-microglobulin (beta 2-m) and its amyloidogenic core peptide, K3, using a high precision densitometer. The transition from the acid-denatured beta 2-m to the mature amyloid fibrils was accompanied by a positive change in the partial specific volume, which was larger than that observed for the transition from the acid-denatured beta(2)-m to the native structure. The data imply that the mature amyloid fibrils are more voluminous than the native structure because of a sparse packing density of side chains. In contrast, the formation of the mature amyloid-like fibrils of the K3 from the random coil was followed by a considerable decrease in the partial specific volume, suggesting a highly compact core structure. Interestingly, the immature amyloid-like fibrils of beta(2)-m exhibited a volume intermediate between those of the mature fibrils of beta(2)- m and K3, because of the core structure at their center and the relatively noncompact region around the core with much hydration. These volumetric differences would result from the nature of main-chain-dominated fibrillogenesis. We suggest comprehensive models for these three types of fibrils illustrating packing and hydrational states.