2FQ8

NMR structure of 2F associated with lipid disc

2FQ8 の概要

• エントリーDOI: 10.2210/pdb2fq8/pdb
• 関連するPDBエントリー: 2FQ5
• 分子名称: 2F (1 entity in total)
• 機能のキーワード: amphipathic helix, class a helix, unknown function
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2229.59

構造登録者

Mishra, V.K.,Anantharamaiah, G.M.,Krishna, N.R. (登録日: 2006-01-17, 公開日: 2006-01-24, 最終更新日: 2024-11-20)

主引用文献

Mishra, V.K.,Anantharamaiah, G.M.,Segrest, J.P.,Palgunachari, M.N.,Chaddha, M.,Sham, S.W.,Krishna, N.R.
Association of a Model Class A (Apolipoprotein) Amphipathic {alpha} Helical Peptide with Lipid: high resolution NMR studies of peptide-lipid discoidal complexes
J.Biol.Chem., 281:6511-6519, 2006

PubMed Abstract: Class A amphipathic helical peptides have been shown to mimic apolipoprotein A-I, the major protein component of high density lipoproteins and have been shown to inhibit atherosclerosis in several dyslipidemic mouse models. Previously we reported the NMR structure of Ac-18A-NH2, the base-line model class A amphipathic helical peptide in a 50% (v/v) trifluoroethanol-d3/water mixture, a membrane-mimic environment (Mishra, V. K., Palgunachari, M. N., Anantharamaiah, G. M., Jones, M. K., Segrest, J. P., and Krishna, N. R. (2001) Peptides 22, 567-573). The peptide Ac-18A-NH2 forms discoidal nascent high density lipoprotein-like particles with 1,2-dimyristoyl-sn-glycero-3-phosphocholine. Because subtle structural changes in the peptide.lipid complexes have been shown to be responsible for their antiatherogenic properties, we undertook high resolution NMR studies to deduce detailed structure of recombinant peptide.1,2-dimyristoyl-sn-glycero-3-phosphocholine complexes. The peptide adopts a well defined amphipathic alpha helical structure in association with the lipid at a 1:1 peptide:lipid weight ratio. Nuclear Overhauser effect spectroscopy revealed a number of intermolecular close contacts between the aromatic residues in the hydrophobic face of the helix and the lipid acyl chain protons. The pattern of observed peptide-lipid nuclear Overhauser effects is consistent with a parallel orientation of the amphipathic alpha helix, with respect to the plane of the lipid bilayer, on the edge of the disc (the belt model). Based on the results of chemical cross-linking and molecular modeling, we propose that peptide helices are arranged in a head to tail fashion to cover the edge of the disc. This arrangement of peptides is also consistent with the pKa values of the Lys residues determined previously. Taken together, these results provide for the first time a high resolution structural view of the peptide.lipid discoidal complexes formed by a class A amphipathic alpha helical peptide.

PubMed: 16407255
DOI: 10.1074/jbc.M511475200

実験手法

SOLUTION NMR