Linked Life Data

12056915

Source:http://linkedlifedata.com/resource/pubmed/id/12056915

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2002-6-11
pubmed:abstractText
The carboxyl terminus of the type-1 angiotensin II receptor (AT(1A)) is a focal point for receptor activation and deactivation. Synthetic peptides corresponding to the membrane-proximal, first 20 amino acids of the carboxyl terminus adopt an alpha-helical conformation in organic solvents, suggesting that the secondary structure of this region may be sensitive to hydrophobic environments. Using surface plasmon resonance, immobilized lipid chromatography, and circular dichroism, we examined whether this positively charged, amphipathic alpha-helical region of the AT(1A) receptor can interact with lipid components in the cell membrane and thereby modulate local receptor attachment and structure. A synthetic peptide corresponding to the proximal region of the AT(1A) receptor carboxyl terminus (Leu(305) to Lys(325)) was shown by surface plasmon resonance to bind with high affinity to the negatively charged lipid, dimyristoyl L-alpha-phosphatidyl-DL-glycerol (DMPG), but poorly to the zwitterionic lipid, dimyristoyl L-alpha-phosphatidylcholine (DMPC). In contrast, a peptide analogue possessing substitutions at four lysine residues (corresponding to Lys(307,308,310,311)) displayed poor association with either lipid, indicating a crucial anionic component to the interaction. Circular dichroism analysis revealed that both the wild-type and substituted peptides possessed alpha-helical propensity in methanol and trifluoroethanol, while the wild-type peptide also adopted partially inserted helical structure in DMPG and DMPC liposomes. In contrast, the substituted peptide exhibited spectra that suggested the presence of beta-sheet and alpha-helical structure in both liposomes. Immobilized lipid chromatography was used to characterize the hydrophobic component of the membrane interaction, and the results demonstrated that hydrophobic and electrostatic interactions mediated the binding of the wild-type peptide but that the substituted peptide bound to the model membranes mainly via hydrophobic forces. We propose that, in intact AT(1A) receptors, the proximal carboxyl terminus associates with the cytoplasmic face of the cell membrane via a high-affinity, anionic phospholipid-specific tethering that serves to increase the amphipathic helicity of this region. Such associations may be important for receptor function and common for G protein-coupled receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7830-40
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12056915-Amino Acid Sequence, pubmed-meshheading:12056915-Anions, pubmed-meshheading:12056915-Binding Sites, pubmed-meshheading:12056915-Chromatography, pubmed-meshheading:12056915-Circular Dichroism, pubmed-meshheading:12056915-Computer Simulation, pubmed-meshheading:12056915-Hydrophobic and Hydrophilic Interactions, pubmed-meshheading:12056915-Models, Molecular, pubmed-meshheading:12056915-Molecular Sequence Data, pubmed-meshheading:12056915-Peptide Fragments, pubmed-meshheading:12056915-Phospholipids, pubmed-meshheading:12056915-Protein Binding, pubmed-meshheading:12056915-Protein Structure, Secondary, pubmed-meshheading:12056915-Receptor, Angiotensin, Type 1, pubmed-meshheading:12056915-Receptors, Angiotensin, pubmed-meshheading:12056915-Static Electricity, pubmed-meshheading:12056915-Surface Plasmon Resonance
pubmed:year
2002
pubmed:articleTitle
Electrostatic and hydrophobic forces tether the proximal region of the angiotensin II receptor (AT1A) carboxyl terminus to anionic lipids.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, P.O. Box 13D, Monash University, Clayton 3800, Victoria, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't