NMR solution structure of human cannabinoid receptor-1 helix 7/8 peptide: Candidate electrostatic interactions and microdomain formation

被引：17

作者：

Tyukhtenko, Sergiy ^{[1
,2
]}

Tiburu, Elvis K. ^{[1
,2
]}

Deshmukh, Lalit ^{[3
]}

Vinogradova, Olga ^{[3
]}

Janero, David R. ^{[1
,2
]}

Makriyannis, Alexandros ^{[1
,2
]}

机构：

[1] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA

[2] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA

[3] Univ Connecticut, Sch Pharm, Dept Pharmaceut Sci, Storrs, CT 06269 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 390卷 / 03期

关键词：

Cannabinergic ligand; G protein-coupled receptor; Interhelical microdomain; Praline kink; Signal transduction; Structural biology; Transmembrane protein; PROTEIN-COUPLED RECEPTORS; MOLECULAR-DYNAMICS; CB1; MODEL; RHODOPSIN; CONFORMATION; ENVIRONMENT; ACTIVATION; STATE; MOTIF;

D O I：

10.1016/j.bbrc.2009.09.053

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We report the NMR solution structure of a synthetic 40-mer (T-377-E-416) that encompasses human cannabinoid receptor-1 (hCB1) transmembrane helix 7 (TMH7) and helix 8 (H8) [hCB1(TMH7/H8)] in 30% trifluoroethanol/H2O. Structural features include, from the peptide's amino terminus, a hydrophobic alpha-helix (TMH7); a loop-like, 11 residue segment featuring a pronounced Pro-kink within the conserved NPxxY motif; a short amphipathic alpha-helix (H8) orthogonal to TMH7 with cationic and hydrophobic amino-acid clusters: and an unstructured C-terminal end. The hCB1(TMH7/H8) NMR solution structure suggests multiple electrostatic amino-acid interactions, including an intrahelical H8 salt bridge and a hydrogen-bond network involving the peptide's loop-like region. Potential cation-pi and cation-phenolic OH interactions between Y-397 in the TMH7 NPxxY motif and R-405 in H8 are identified as candidate structural forces promoting interhelical microdomain formation. This microdomain may function as a flexible molecular hinge during ligand-induced hCB1 conformer transitions. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：441 / 446

页数：6

共 39 条

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