2nzz: Difference between revisions

Revision as of 19:13, 21 February 2008

NMR structure analysis of the Penetratin conjugated Gas (374-394) peptide

OverviewOverview

A42 is a chimera peptide consisting of Galphas(374-394)C379A--the 21-mer C terminus of the Galphas protein, able of adenosine inhibitory activity--and penetratin--the 16 residue fragment, derived from the homeodomain of the Drosophila transcription factor Antennapedia. A42 is able to cross cell membranes and to inhibit A2A and A2B adenosine and beta-adrenergic receptor stimulated camps (D'Ursi et al. Mol. Pharmacol. 2006, 69, 727-36). Here we present an extensive biophysical study of A42 in different membrane mimetics, with the objective to evaluate the molecular mechanisms which promote the membrane permeation. Fluorescence, CD, and NMR data were acquired in the presence of negatively charged and zwitterionic sodium dodecyl sulfate and dodecylphosphocholine surfactants. To validate the spectroscopic results in a larger scale, fluorescence microscopy experiments were performed on negatively charged and zwitterionic dipalmitoylphosphatidylglycerol and dipalmitoylphosphatidylcholine vesicles. Our results show that the internalization of A42 is mainly driven by electrostatic interactions, hydrophobic interactions playing only a secondary, sinergistic role. The distribution of the charges along the molecule has an important role, highlighting that internalization is a process which requires a specific matching of peptide and membrane properties.

About this StructureAbout this Structure

2NZZ is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.

ReferenceReference

Driving forces in the delivery of penetratin conjugated G protein fragment., Albrizio S, Giusti L, D'Errico G, Esposito C, Porchia F, Caliendo G, Novellino E, Mazzoni MR, Rovero P, D'Ursi AM, J Med Chem. 2007 Apr 5;50(7):1458-64. Epub 2007 Mar 10. PMID:17348636

Page seeded by OCA on Thu Feb 21 18:12:56 2008

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OCA

@@ Line 4: / Line 4: @@
 ==Overview==
-A42 is a chimera peptide consisting of Galphas(374-394)C379A--the 21-mer C, terminus of the Galphas protein, able of adenosine inhibitory, activity--and penetratin--the 16 residue fragment, derived from the, homeodomain of the Drosophila transcription factor Antennapedia. A42 is, able to cross cell membranes and to inhibit A2A and A2B adenosine and, beta-adrenergic receptor stimulated camps (D'Ursi et al. Mol. Pharmacol., 2006, 69, 727-36). Here we present an extensive biophysical study of A42, in different membrane mimetics, with the objective to evaluate the, molecular mechanisms which promote the membrane permeation. Fluorescence, CD, and NMR data were acquired in the presence of negatively charged and, zwitterionic sodium dodecyl sulfate and dodecylphosphocholine surfactants., To validate the spectroscopic results in a larger scale, fluorescence, microscopy experiments were performed on negatively charged and, zwitterionic dipalmitoylphosphatidylglycerol and, dipalmitoylphosphatidylcholine vesicles. Our results show that the, internalization of A42 is mainly driven by electrostatic interactions, hydrophobic interactions playing only a secondary, sinergistic role. The, distribution of the charges along the molecule has an important role, highlighting that internalization is a process which requires a specific, matching of peptide and membrane properties.
+A42 is a chimera peptide consisting of Galphas(374-394)C379A--the 21-mer C terminus of the Galphas protein, able of adenosine inhibitory activity--and penetratin--the 16 residue fragment, derived from the homeodomain of the Drosophila transcription factor Antennapedia. A42 is able to cross cell membranes and to inhibit A2A and A2B adenosine and beta-adrenergic receptor stimulated camps (D'Ursi et al. Mol. Pharmacol. 2006, 69, 727-36). Here we present an extensive biophysical study of A42 in different membrane mimetics, with the objective to evaluate the molecular mechanisms which promote the membrane permeation. Fluorescence, CD, and NMR data were acquired in the presence of negatively charged and zwitterionic sodium dodecyl sulfate and dodecylphosphocholine surfactants. To validate the spectroscopic results in a larger scale, fluorescence microscopy experiments were performed on negatively charged and zwitterionic dipalmitoylphosphatidylglycerol and dipalmitoylphosphatidylcholine vesicles. Our results show that the internalization of A42 is mainly driven by electrostatic interactions, hydrophobic interactions playing only a secondary, sinergistic role. The distribution of the charges along the molecule has an important role, highlighting that internalization is a process which requires a specific matching of peptide and membrane properties.
 ==About this Structure==
@@ Line 13: / Line 13: @@
 [[Category: Protein complex]]
 [[Category: Albrizio, S.]]
-[[Category: Errico, G.D.]]
+[[Category: Errico, G D.]]
 [[Category: Espsito, C.]]
 [[Category: Novellino, E.]]
 [[Category: Rovero, P.]]
-[[Category: Ursi, A.M.D.]]
+[[Category: Ursi, A M.D.]]
 [[Category: a2a adenosine receptor]]
 [[Category: cell-penetrating peptides]]
@@ Line 26: / Line 26: @@
 [[Category: penetratin]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:01:00 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:12:56 2008''