Related ArticlesPhosphorylation-induced structural changes in the amyloid precursor protein cytoplasmic tail detected by NMR.
J Mol Biol. 2001 Mar 30;307(3):871-84
Authors: Ramelot TA, Nicholson LK
The cytoplasmic tail of the amyloid precursor protein (APPc) interacts with several cellular factors implicated in intracellular signaling or proteolytic production of amyloid beta peptide found in senile plaques of Alzheimer's disease patients. APPc contains two threonine residues (654 and 668 relative to APP695, or 6 and 20 relative to APPc) and a serine residue (655 or 7, respectively) that are known to be phosphorylated in vivo and may play regulatory roles in these events. We show by solution NMR spectroscopy of a 49 residue cytoplasmic tail peptide (APP-C) that in all three cases, phosphorylation induces changes in backbone dihedral angles that can be attributed to formation of local hydrogen bonds between the phosphate group and nearby amide protons. Phosphorylation of S7 also induces chemical shift changes in the hydrophobic cluster (residues I8-V13), indicating additional medium-range effects. The most pronounced changes occur upon phosphorylation of T20, a neuron-specific phosphorylation site, where the N-terminal helix capping box previously characterized for this region is altered. Characterization of torsion angles and transient hydrogen bonds indicates that prolyl isomerization of the pThr-Pro peptide bond results from both destabilization of the N-terminal helix capping box and stabilization of the cis isomer by transient hydrogen bonds. The significant population of the cis isomer (9 %) present after phosphorylation of T20 suggests a potential role of selective recognition of cis versus trans isomers in response to phosphorylation of APP. Together, these structural changes indicate that phosphorylation may act as a conformational switch in the cytoplasmic tail of APP to alter specificity and affinity of binding to cytosolic partners, particularly in response to the abnormal phosphorylation events associated with Alzheimer's disease.
Expression, purification, and reconstitution of the transmembrane domain of the human amyloid precursor protein for NMR studies.
Expression, purification, and reconstitution of the transmembrane domain of the human amyloid precursor protein for NMR studies.
Expression, purification, and reconstitution of the transmembrane domain of the human amyloid precursor protein for NMR studies.
Protein Expr Purif. 2011 Aug 31;
Authors: Chen W, Gamache E, Richardson D, Du Z, Wang C
Abstract
Alzheimer's disease (AD) is the most common type of dementia in elderly people. Senile plaques, a pathologic hallmark of AD, are composed of amyloid ? peptide (A?). A? aggregation produces...
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09-13-2011 08:27 PM
Evidence from solid-state NMR for nonhelical conformations in the transmembrane domain of the amyloid precursor protein.
Evidence from solid-state NMR for nonhelical conformations in the transmembrane domain of the amyloid precursor protein.
Evidence from solid-state NMR for nonhelical conformations in the transmembrane domain of the amyloid precursor protein.
Biophys J. 2011 Feb 2;100(3):711-9
Authors: Lu JX, Yau WM, Tycko R
The amyloid precursor protein (APP) is subject to proteolytic processing by ?-secretase within neuronal membranes, leading to Alzheimer's disease-associated ?-amyloid peptide production by cleavage near the midpoint of the*single...
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02-02-2011 12:40 PM
[NMR paper] Simplification of protein NOESY spectra using bioorganic precursor synthesis and NMR
Simplification of protein NOESY spectra using bioorganic precursor synthesis and NMR spectral editing.
Related Articles Simplification of protein NOESY spectra using bioorganic precursor synthesis and NMR spectral editing.
J Am Chem Soc. 2004 May 5;126(17):5348-9
Authors: Lichtenecker R, Ludwiczek ML, Schmid W, Konrat R
A novel method is proposed for the analysis of protein NOEs in solution. In this approach, chemically synthesized precursor compounds for the amino acids valine, leucine, and isoleucine are used for amino acid specific labeling...
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11-24-2010 09:51 PM
[NMR paper] Ligand-induced structural changes to maltodextrin-binding protein as studied by solut
Ligand-induced structural changes to maltodextrin-binding protein as studied by solution NMR spectroscopy.
Related Articles Ligand-induced structural changes to maltodextrin-binding protein as studied by solution NMR spectroscopy.
J Mol Biol. 2001 Jun 15;309(4):961-74
Authors: Evenäs J, Tugarinov V, Skrynnikov NR, Goto NK, Muhandiram R, Kay LE
Solution NMR studies on the physiologically relevant ligand-free and maltotriose-bound states of maltodextrin-binding protein (MBP) are presented. Together with existing data on MBP in complex with...
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11-19-2010 08:32 PM
[NMR paper] Phosphorylation-induced torsion-angle strain in the active center of HPr, detected by
Phosphorylation-induced torsion-angle strain in the active center of HPr, detected by NMR and restrained molecular dynamics refinement.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www3.interscience.wiley.com-aboutus-images-wiley_interscience_pubmed_logo_FREE_120x27.gif http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.pubmedcentral.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.gif Related Articles Phosphorylation-induced torsion-angle strain in the active center of HPr, detected by NMR and restrained molecular dynamics refinement.
Protein Sci. 1996...
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08-22-2010 02:27 PM
[NMR paper] Structural consequences of histidine phosphorylation: NMR characterization of the pho
Structural consequences of histidine phosphorylation: NMR characterization of the phosphohistidine form of histidine-containing protein from Bacillus subtilis and Escherichia coli.
Related Articles Structural consequences of histidine phosphorylation: NMR characterization of the phosphohistidine form of histidine-containing protein from Bacillus subtilis and Escherichia coli.
Biochemistry. 1994 Dec 27;33(51):15271-82
Authors: Rajagopal P, Waygood EB, Klevit RE
The bacterial phosphoenolpyruvate:sugar phosphotransferase system involves a series...
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08-22-2010 03:29 AM
[NMR paper] Light-induced membrane protein phosphorylation in the bovine rod outer segment. A mag
Light-induced membrane protein phosphorylation in the bovine rod outer segment. A magic angle spinning 31P-NMR study.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles Light-induced membrane protein phosphorylation in the bovine rod outer segment. A magic angle spinning 31P-NMR study.
Biophys Chem. 1990 May;36(1):27-31
Authors: Albert AD, Frye JS, Yeagle PL
Magic angle spinning 31P-NMR (MAS 31P-NMR) spectra of bovine rod outer segments, unphosphorylated and...
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08-21-2010 10:48 PM
[NMR paper] The mitochondrial precursor protein apocytochrome c strongly influences the order of
The mitochondrial precursor protein apocytochrome c strongly influences the order of the headgroup and acyl chains of phosphatidylserine dispersions. A 2H and 31P NMR study.
Related Articles The mitochondrial precursor protein apocytochrome c strongly influences the order of the headgroup and acyl chains of phosphatidylserine dispersions. A 2H and 31P NMR study.
Biochemistry. 1990 Mar 6;29(9):2312-21
Authors: Jordi W, de Kroon AI, Killian JA, de Kruijff B
Deuterium and phosphorus nuclear magnetic resonance techniques were used to study the...
Phosphorylation-induced structural changes in the amyloid precursor protein cytoplasm
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