Towards Understanding the Structure-Function Relationship of Human Amyloid Disease

Author(s): Chris Dealwis, Jonathan Wall.

Journal Name: Current Drug Targets

Volume 5 , Issue 2 , 2004

Abstract:

Immunoglobulin light chain (LC) proteins exhibit the greatest sequence variability of all proteins associated with amyloid disease. The hallmark event in amyloidogenesis is a change in the secondary and / /or tertiary structure of a normal, soluble protein, that fosters selfaggregation and fibril formation. The structural heterogeneity of light chain proteins has hampered understanding of the precise mechanisms involved in fibril formation. The development of effective therapeutics will be benefited by a fundamental understanding of mechanisms and structural prerequisites which govern amyloidogenesis. This review focuses on light chain (AL) amyloidosis resulting from the aggregation of κ and λ LCs. Specifically the thermodynamic and structural data of several WT and mutant amyloidogenic LCs have been carefully examined. Moreover, we discuss the importance of hydrophobic and ionic interactions on amyloidosis by comparing several available three-dimensional structures of amyloidogenic and highly homologous non-amyloidogenic proteins that can be destabilized to become amyloidogenic by site specific mutations.

Keywords: Human Amyloid Disease, non-amyloidogenic proteins, thermodynamic, amyloidogenesis

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Article Details

VOLUME: 5
ISSUE: 2
Year: 2004
Page: [159 - 171]
Pages: 13
DOI: 10.2174/1389450043490550
Price: $58

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