Cellular membranes and lipid-binding domains as attractive targets for drug development

Date
2008-08
Language
American English
Embargo Lift Date
Committee Members
Degree
Degree Year
Department
Grantor
Journal Title
Journal ISSN
Volume Title
Found At
Bentham Science Publishers
Abstract

Interdisciplinary research focused on biological membranes has revealed them as signaling and trafficking platforms for processes fundamental to life. Biomembranes harbor receptors, ion channels, lipid domains, lipid signals, and scaffolding complexes, which function to maintain cellular growth, metabolism, and homeostasis. Moreover, abnormalities in lipid metabolism attributed to genetic changes among other causes are often associated with diseases such as cancer, arthritis and diabetes. Thus, there is a need to comprehensively understand molecular events occurring within and on membranes as a means of grasping disease etiology and identifying viable targets for drug development. A rapidly expanding field in the last decade has centered on understanding membrane recruitment of peripheral proteins. This class of proteins reversibly interacts with specific lipids in a spatial and temporal fashion in crucial biological processes. Typically, recruitment of peripheral proteins to the different cellular sites is mediated by one or more modular lipid-binding domains through specific lipid recognition. Structural, computational, and experimental studies of these lipid-binding domains have demonstrated how they specifically recognize their cognate lipids and achieve subcellular localization. However, the mechanisms by which these modular domains and their host proteins are recruited to and interact with various cell membranes often vary drastically due to differences in lipid affinity, specificity, penetration as well as protein-protein and intramolecular interactions. As there is still a paucity of predictive data for peripheral protein function, these enzymes are often rigorously studied to characterize their lipid-dependent properties. This review summarizes recent progress in our understanding of how peripheral proteins are recruited to biomembranes and highlights avenues to exploit in drug development targeted at cellular membranes and/or lipid-binding proteins.

Description
item.page.description.tableofcontents
item.page.relation.haspart
Cite As
Sudhahar, C. G., Haney, R. M., Xue, Y., & Stahelin, R. V. (2008). Cellular membranes and lipid-binding domains as attractive targets for drug development. Current drug targets, 9(8), 603-13.
ISSN
Publisher
Series/Report
Sponsorship
Major
Extent
Identifier
Relation
Journal
Current Drug Targets
Rights
Publisher Policy
Source
PMC
Alternative Title
Type
Article
Number
Volume
Conference Dates
Conference Host
Conference Location
Conference Name
Conference Panel
Conference Secretariat Location
Version
Author's manuscript
Full Text Available at
This item is under embargo {{howLong}}