2KOE

Human cannabinoid receptor 1 - helix 7/8 peptide

Summary for 2KOE

• Entry DOI: 10.2210/pdb2koe/pdb
• NMR Information: BMRB: 16504
• Descriptor: human cannabinoid receptor 1 - helix 7/8 peptide (1 entity in total)
• Functional Keywords: gpcr, hcb1, membrane protein, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Multi-pass membrane protein: P21554
• Total number of polymer chains: 1
• Total formula weight: 4524.31

Authors

Deshmukh, L.,Vinogradova, O.,Makriyannis, A.,Tiburu, E.,Tyukhtenko, S.,Janero, D. (deposition date: 2009-09-18, release date: 2009-10-06, Last modification date: 2024-05-22)

Primary citation

Tyukhtenko, S.,Tiburu, E.K.,Deshmukh, L.,Vinogradova, O.,Janero, D.R.,Makriyannis, A.
NMR solution structure of human cannabinoid receptor-1 helix 7/8 peptide: candidate electrostatic interactions and microdomain formation.
Biochem.Biophys.Res.Commun., 390:441-446, 2009

PubMed Abstract: 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/H(2)O. 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.

PubMed: 19766594
DOI: 10.1016/j.bbrc.2009.09.053

Experimental method

SOLUTION NMR