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Protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structural data

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 techn...

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Autores principales: Scott, David L, Diez, Gerold, Goldmann, Wolfgang H
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1523333/
https://www.ncbi.nlm.nih.gov/pubmed/16569237
http://dx.doi.org/10.1186/1742-4682-3-17
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author Scott, David L
Diez, Gerold
Goldmann, Wolfgang H
author_facet Scott, David L
Diez, Gerold
Goldmann, Wolfgang H
author_sort Scott, David L
collection PubMed
description 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 alpha-helix 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 identified, and whether use of the algorithm can be safely extended to other classes of proteins, will require further mapping of these sites, including genetic manipulation and/or targeted crystallography.
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spelling pubmed-15233332006-07-28 Protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structural data Scott, David L Diez, Gerold Goldmann, Wolfgang H Theor Biol Med Model Review 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 alpha-helix 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 identified, and whether use of the algorithm can be safely extended to other classes of proteins, will require further mapping of these sites, including genetic manipulation and/or targeted crystallography. BioMed Central 2006-03-28 /pmc/articles/PMC1523333/ /pubmed/16569237 http://dx.doi.org/10.1186/1742-4682-3-17 Text en Copyright © 2006 Scott et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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.
spellingShingle Review
Scott, David L
Diez, Gerold
Goldmann, Wolfgang H
Protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structural data
title Protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structural data
title_full Protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structural data
title_fullStr Protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structural data
title_full_unstemmed Protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structural data
title_short Protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structural data
title_sort protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structural data
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1523333/
https://www.ncbi.nlm.nih.gov/pubmed/16569237
http://dx.doi.org/10.1186/1742-4682-3-17
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