Protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structu
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BioMed Central
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Protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structural data David L Scott*1, Gerold Diez2 and Wolfgang H Goldmann*1,2 Address: 1Renal Unit, Leukocyte Biology & Inflammation Program, Structural Biology Program and the Massachusetts General Hospital/Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA and 2Friedrich-Alexander-University of Erlangen-Nuremberg, Center for Medical Physics and Technology, Biophysics Group, Henkestrasse 91, 91052 Erlangen, Germany Email: David L Scott* - [email protected]; Gerold Diez - [email protected]; Wolfgang H Goldmann* - [email protected] * Corresponding authors
Published: 28 March 2006 Theoretical Biology and Medical Modelling 2006, 3:17
doi:10.1186/1742-4682-3-17
Received: 21 November 2005 Accepted: 28 March 2006
This article is available from: http://www.tbiomed.com/content/3/1/17 © 2006 Scott et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: Over the past decade our laboratory has focused on understanding how soluble cytoskeleton-associated proteins interact with membranes and other lipid aggregates. Many protein domains mediating specific cell membrane interactions appear by fluorescence microscopy and other precision techniques to be partially inserted into the lipid bilayer. It is unclear whether these protein-lipid-interactions are dependent on shared protein motifs or unique regional physiochemistry, or are due to more global characteristics of the protein. Results: We have developed a novel computational program that predicts a protein's lipid-binding site(s) from primary sequence data. Hydrophobic labeling, Fourier transform infrared spectroscopy (FTIR), film balance, T-jump, CD spectroscopy and calorimetry experiments confirm that the interfaces predicted for several key cytoskeletal proteins (alpha-actinin, Arp2, CapZ, talin and vinculin) partially insert into lipid aggregates. The validity of these predictions is supported by an analysis of the available three-dimensional structural data. The lipid interfaces predicted by our algorithm generally contain energetically favorable secondary structures (e.g., an amphipathic alphahelix flanked by a flexible hinge or loop region), are solvent-exposed in the intact protein, and possess favorable local or global electrostatic properties. Conclusion: At present, there are few reliable methods to determine the region of a protein that mediates biologically important interactions with lipids or lipid aggregates. Our matrix-based algorithm predicts lipid interaction sites that are consistent with the available biochemical and structural data. To determine whether these sites are indeed correctly identifi
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