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Biochim Biophys Acta. 2012 Apr;1818(4):1115-22. doi: 10.1016/j.bbamem.2011.07.046. Epub 2011 Aug 5.

Membrane protein misassembly in disease.

Author information

1
Division of Molecular Structure & Function, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.

Abstract

Helix-helix interactions play a central role in the folding and assembly of integral α-helical membrane proteins and are fundamentally dictated by the amino acid sequence of the TM domain. It is not surprising then that missense mutations that target these residues are often linked to disease. In this review, we focus on the molecular mechanisms through which missense mutations lead to aberrant folding and/or assembly of these proteins, and then discuss pharmacological approaches that may potentially mitigate or reverse the negative effects of these mutations. Improving our understanding of how missense mutations affect the interactions between TM α-helices will increase our capability to develop effective therapeutic approaches to counter the misassembly of these proteins and, ultimately, disease. This article is part of a Special Issue entitled: Protein Folding in Membranes.

PMID:
21840297
DOI:
10.1016/j.bbamem.2011.07.046
[Indexed for MEDLINE]
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