Towards understanding the structure-function relationship of human amyloid disease

Chris Dealwis, Jonathan Wall

Research output: Contribution to journalReview article

25 Citations (Scopus)

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 or a normal, soluble protein, that fosters self-aggregation 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.

Original languageEnglish (US)
Pages (from-to)159-171
Number of pages13
JournalCurrent Drug Targets
Volume5
Issue number2
DOIs
StatePublished - Feb 1 2004

Fingerprint

Amyloid
Amyloidosis
Proteins
Agglomeration
Immunoglobulin Light Chains
Light
Hydrophobic and Hydrophilic Interactions
Thermodynamics
Mutation
Therapeutics

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Towards understanding the structure-function relationship of human amyloid disease. / Dealwis, Chris; Wall, Jonathan.

In: Current Drug Targets, Vol. 5, No. 2, 01.02.2004, p. 159-171.

Research output: Contribution to journalReview article

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