title: Amyloid fibril formation by a domain of rat cell adhesion molecule.
abstract: Amyloid fibrils are protein aggregates implicated in several amyloidotic diseases. Cellular membranes with local decrease in pH and dielectric constant are associated with the amyloid formation. In this study, domain 1 of cell adhesion molecule CD2 (CD2-1) is used for studying amyloid fibril formation in a water/trifluoroethanol (TFE) mixture. CD2-1 is an all beta-sheet protein similar in topology to the amyloidogenic light chain variable domain, which deposits as amyloid in light chain amyloidosis at acidic pH. When incubated at pH 2.0 in the presence of 18% TFE, CD2-1 initiates the process to assemble into amyloid fibrils. It has been shown that TFE induces CD2-1 conformational change with a chemical transition (C(m)) of 18% (v/v). ANS (1-anilinonapthalene-8-sulfonic acid) binding was used to show that the hydrophobic surface becomes exposed under these solvent conditions. Our studies indicate that partial formation of a non-native conformation and the exposure of the hydrophobic interior could be the origins of oligomerization and fibril formation of CD2-1.
authors.affiliation: Department of Chemistry, Center of Drug Design, Georgia State University, Atlanta, GA, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Carroll
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Yiming
authors.initials: Y
authors.lastname: Ye
authors.forename: Robert
authors.initials: R
authors.lastname: Simmons
authors.forename: Jenny J
authors.initials: JJ
authors.lastname: Yang
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D000817:Anilino Naphthalenesulfonates; D000818:Animals; D018801:CD2 Antigens / Q000737:chemistry*; D004926:Escherichia coli; D011138:Polytetrafluoroethylene; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051381:Rats; D013057:Spectrum Analysis; D014867:Water
chemical_list: D000682:Amyloid; D000817:Anilino Naphthalenesulfonates; D018801:CD2 Antigens; C465878:Cd2 protein, rat; D014867:Water; D011138:Polytetrafluoroethylene