NR AELW
AU Gazit,E.
TI A possible role for pi-stacking in the self-assembly of amyloid fibrils
QU The FASEB Journal 2002 Jan; 16(1): 77-83
PT journal article
AB Amyloid fibril formation is assumed to be the molecular basis for a variety of diseases of unrelated origin. Despite its fundamental clinical importance, the mechanism of amyloid formation is not fully understood. When we analyzed a variety of short functional fragments from unrelated amyloid-forming proteins, a remarkable occurrence of aromatic residues was observed. The finding of aromatic residues in diverse fragments raises the possibility that pi-pi interactions may play a significant role in the molecular recognition and self-assembly processes that lead to amyloid formation. This is in line with the well-known central role of pi-stacking interactions in self-assembly processes in the fields of chemistry and biochemistry. We speculate that the stacking interactions may provide energetic contribution as well as order and directionality in the self-assembly of amyloid structures. Experimental data regarding amyloid formation and inhibition by short peptide analogs also support our hypothesis. The pi-stacking hypothesis suggests a new approach to understanding the self-assembly mechanism that governs amyloid formation and indicates possible ways to control this process.
MH Alzheimer Disease/etiology; Amino Acid Sequence; Amino Acids, Aromatic/chemistry; Amyloid/*biosynthesis/*chemistry; Amyloid beta-Protein/chemistry; Amyloidosis/metabolism; Animal; Fungal Proteins/chemistry; Glycoproteins/chemistry; Human; *Models, Chemical; Peptide Fragments/chemistry; Prions/chemistry
AD Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, Tel Aviv 69978, Israel. ehudg@post.tau.ac.il
SP englisch
PO USA