Organic solvent mediated self-association of an amyloid forming peptide from beta2-microglobulin: an atomic force microscopy study.
Human beta(2)-microglobulin (beta(2)m) forms amyloid fibrils in hemodialysis related amyloidosis. Peptides spanning the beta strands of beta(2)m have been shown to form amyloid fibrils in isolation. We have studied the self-association of a 13-residue peptide Ac-DWSFYLLYYTEFT-am (Pbeta(2)m) spanning one of the beta-strands of human beta(2)-microglobulin when dissolved in various organic solvents such as methanol (MeOH), trifluoroethanol (TFE), hexafluoroisopropanol (HFIP), and dimethylsulfoxide. We have observed that Pbeta(2)m forms amyloid fibrils when diluted from organic solvents into aqueous buffer at pH 7.0 as judged by increase in thioflavin T fluorescence. Fibril formation was observed to depend on the solvents in which peptide stock solutions were prepared. Circular dichroism spectra indicated propensity for helical conformation in MeOH, TFE, and HFIP. In buffer, beta-structure was observed irrespective of the solvent in which the peptide stock solutions were prepared. Atomic force microscopy images obtained by drying the peptide on mica from organic solvents indicated the ability of Pbeta(2)m to self-associate to form nonfibrillar structures. Morphology of the structures was dependent on the solvent in which the peptide was dissolved. Peptides that have the ability to self-associate such as amyloid-forming peptides would be attractive candidates for the generation of self-assembled structures with varying morphologies by appropriate choice of surfaces and solvents for dissolution.
Chaudhary
Nitin
N
Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad 500 007, India.
Singh
Shashi
S
Nagaraj
Ramakrishnan
R
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D000686:Amyloidosis / Q000378:metabolism; D002942:Circular Dichroism; D006801:Humans; D018625:Microscopy, Atomic Force; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D006435:Renal Dialysis; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D001613:beta 2-Microglobulin / Q000737:chemistry*
D000682:Amyloid; D010455:Peptides; D012997:Solvents; D001613:beta 2-Microglobulin