Structural biology of human cannabinoid receptor-2 helix 6 in membrane-mimetic environments.
We detail the structure and dynamics of a synthetic peptide corresponding to transmembrane helix 6 (TMH6) of human cannabinoid receptor-2 (hCB2) in biomembrane-mimetic environments. The peptide's NMR structural biology is characterized by two alpha-helical domains bridged by a flexible, nonhelical hinge region containing a highly-conserved CWFP motif with an environmentally sensitive, Pro-based conformational switch. Buried within the peptide's flexible region, W(258) may hydrogen-bond with L(255) to help stabilize the Pro-kinked hCB2 TMH6 structure and position C(257) advantageously for interaction with agonist ligands. These characteristics of hCB2 TMH6 are potential structural features of ligand-induced hCB2 activation in vivo.
Tiburu
Elvis K
EK
Center for Drug Discovery and Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115-5000, USA.
Tyukhtenko
Sergiy
S
Deshmukh
Lalit
L
Vinogradova
Olga
O
Janero
David R
DR
Makriyannis
Alexandros
A
D000595:Amino Acid Sequence; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000737:chemistry*; D014364:Tryptophan / Q000737:chemistry
D008024:Ligands; D010455:Peptides; D043885:Receptor, Cannabinoid, CB2; D014364:Tryptophan