Conformational change and assembly through edge beta strands in transthyretin and other amyloid proteins.

Department of Chemistry and Biochemistry, University of California-Los Angeles (UCLA), Post Office Box 951569, Los Angeles, CA 90095-1569, USA.

Numerous diseases are characterized by the formation of insoluble, amyloid protein fibrils. Intensive investigations are beginning to unravel the detailed molecular and structural principles that underlie the spontaneous formation of these fibrils. The amyloid protein transthyretin serves as an excellent system for dissecting the conformational changes and ensuing subunit-subunit associations that lead to amyloid. One working model for tranthyretin amyloid involves the exposure of an "unprotected" edge beta strand, followed by symmetric assembly of subunits to give head-to-head and tail-to-tail protofibrils. The models and principles emerging from studies on transthyretin lead to connections to other amyloid systems.

PMID: 16981673 [PubMed - indexed for MEDLINE]