Structural features of the apelin receptor N-terminal tail and first transmembrane segment implicated in ligand binding and receptor trafficking
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Graphical abstract
Highlights
► We present the structure of the N-terminal portion of the human apelin receptor (AR). ► Combining NMR data and MD simulation, we place this in the full-length AR context. ► The first transmembrane helix of AR is a kinked helix and is required for trafficking. ► The AR N-terminal tail has an anionic surface ideal for binding its ligand, apelin. ► This is one of the first structural characterizations of a peptide-activated GPCR.
Abbreviations
AR
apelin receptor
AR55
residues 1–55 of AR
BSA
bovine serum albumin
CSI
chemical shift index
DMEM
Dulbecco's modified eagle medium
DPC
dodecylphosphocholine
DPPC
dipalmitoylphosphatidylcholine
DSS
sodium 2,2-dimethyl-2-silapentane-5-sulfonate
DTT
dithitothreitol
ERK
extracellular signal-regulated kinase
FBS
fetal bovine serum
GPCR
G-protein coupled receptor
HA
hemagglutinin
HEK
human embryonic kidney
HSQC
heteronuclear single quantum coherence
IPTG
isopropyl β-D-1-thiogalactopyranoside
LB
Luria broth
MD
molecular dynamics
NMR
nuclear magnetic resonance
NOE
nuclear Overhauser enhancement
NOESY
NOE spectroscopy
PCR
polymerase chain reaction
PEI
polyethylenimine
PDB
Protein Data Bank
RMSD
root mean square deviation
TFA
trifluoracetic acid
TM
transmembrane
TOCSY
total correlation spectroscopy
Keywords
Apelin receptor
Membrane protein structure
Divide and conquer
Biomolecular NMR spectroscopy
Homology model
Molecular dynamics simulations
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Copyright © 2013 Elsevier B.V.