Structural biology of human cannabinoid receptor-2 helix 6 in membrane-mimetic environments

Elvis K. Tiburu; Sergiy Tyukhtenko; Lalit Deshmukh; Olga Vinogradova; David R. Janero; Alexandros Makriyannis

doi:10.1016/j.bbrc.2009.04.099

Structural biology of human cannabinoid receptor-2 helix 6 in membrane-mimetic environments

Elvis K. Tiburu, Sergiy Tyukhtenko, Lalit Deshmukh, Olga Vinogradova, David R. Janero, Alexandros Makriyannis

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

Abstract

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 α-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, W²⁵⁸ may hydrogen-bond with L²⁵⁵ to help stabilize the Pro-kinked hCB2 TMH6 structure and position C²⁵⁷ advantageously for interaction with agonist ligands. These characteristics of hCB2 TMH6 are potential structural features of ligand-induced hCB2 activation in vivo.

Original language	English
Pages (from-to)	243-248
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	384
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2009.04.099
Publication status	Published - 26 Jun 2009
Externally published	Yes

Keywords

Agonist ligand
Conformational switch
G protein-coupled receptor
High-resolution NMR
Peptide helix
Proline
Spectrofluorometry
Structural biology
Transmembrane protein
Tryptophan

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10.1016/j.bbrc.2009.04.099

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title = "Structural biology of human cannabinoid receptor-2 helix 6 in membrane-mimetic environments",

abstract = "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 α-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, W258 may hydrogen-bond with L255 to help stabilize the Pro-kinked hCB2 TMH6 structure and position C257 advantageously for interaction with agonist ligands. These characteristics of hCB2 TMH6 are potential structural features of ligand-induced hCB2 activation in vivo.",

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author = "Tiburu, \{Elvis K.\} and Sergiy Tyukhtenko and Lalit Deshmukh and Olga Vinogradova and Janero, \{David R.\} and Alexandros Makriyannis",

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doi = "10.1016/j.bbrc.2009.04.099",

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AU - Tiburu, Elvis K.

AU - Tyukhtenko, Sergiy

AU - Deshmukh, Lalit

AU - Vinogradova, Olga

AU - Janero, David R.

AU - Makriyannis, Alexandros

PY - 2009/6/26

Y1 - 2009/6/26

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AB - 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 α-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, W258 may hydrogen-bond with L255 to help stabilize the Pro-kinked hCB2 TMH6 structure and position C257 advantageously for interaction with agonist ligands. These characteristics of hCB2 TMH6 are potential structural features of ligand-induced hCB2 activation in vivo.

KW - Agonist ligand

KW - Conformational switch

KW - G protein-coupled receptor

KW - High-resolution NMR

KW - Peptide helix

KW - Proline

KW - Spectrofluorometry

KW - Structural biology

KW - Transmembrane protein

KW - Tryptophan

UR - https://www.scopus.com/pages/publications/65549091123

U2 - 10.1016/j.bbrc.2009.04.099

DO - 10.1016/j.bbrc.2009.04.099

M3 - Article

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AN - SCOPUS:65549091123

SN - 0006-291X

VL - 384

SP - 243

EP - 248

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 2

ER -

Structural biology of human cannabinoid receptor-2 helix 6 in membrane-mimetic environments

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Keywords

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