Critical Balance of Electrostatic and Hydrophobic Interactions Is Required for β2-Microglobulin Amyloid Fibril Growth and Stability

• DOI: 10.1021/bi048029t
• Publication Date: 2005-01-25T05:24:31Z
• Authors: Bakthisaran Raman; Eri Chatani; Miho Kihara; Tadato Ban; Miyo Sakai; Kazuhiro Hasegawa; Hironobu Naiki; Ch Mohan Rao; Yuji Goto
• Keywords: Beta-2 microglobulin; Amyloid (mycology); Hydrophobic effect; Static electricity

Investigation of factors that modulate amyloid formation proteins is important to understand and mitigate amyloid-related diseases. To the role electrostatic interactions effect ionic cosolutes, especially anions, on formation, we have investigated salts such as NaCl, NaI, NaClO(4), Na(2)SO(4) fibril growth beta(2)-microglobulin, protein involved in dialysis-related amyloidosis. Under acidic conditions, these exhibit characteristic optimal concentrations where favored. The presence leads an increase hydrophobicity reported by 8-anilinonaphthalene-1-sulfonic acid, indicating anion interaction necessary hydrophobic balance critical for formation. However, high tilt hydrophobicity, leading partitioning amorphous aggregates. Such aggregates are not competent growth. order anions based lowest concentration at which favored SO(4)(2)(-) > ClO(4)(-) I(-) Cl(-), consistent with their electroselectivity series, suggesting preferential binding, rather than general strength effect, plays Anion binding also found stabilize fibrils under condition. Interestingly, sulfate promotes beta(2)-microglobulin pH between 5 6, closer its isoelectric point. Considering earlier studies glycosaminoglycans proteoglycans (i.e., sulfated polyanions) our study suggests ions amyloidogenic may biological significance.