Comparison of β1-adrenergic receptor with rhodopsin,
β2-adrenergic receptor, and A2A adenosine receptor
structures. The turkey β1-adrenergic receptor was mutated to
facilitate its crystallization. The mutated receptor evidenced enhanced
thermostability and preferentially existed in an antagonist-binding state.
Stretches of amino acid sequence were deleted from the N-terminal region
(i.e., the loop connecting helices V and VI and the C-terminal region). A, the
β1-adrenergic receptor is colored by helix: helix I (blue),
helix II (cyan), helix III (violet), helix IV (red), helix V (orange), helix
VI (yellow), helix VII (green), and helix VIII (magenta). Thermostabilizing
mutations (R68S, M90V, Y227A, A282L (not resolved in the shown structure),
F327A, and F338M) and those that either increased functional expression
(C116L) or eliminated a palmitoylation site (C358A) are shown as balls/sticks.
B, structure of the β1-adrenergic receptor (colored by helix)
is shown with bovine rhodopsin (green ribbon) to illustrate key structural
differences. Despite some differences in the transmembrane helices, the main
distinction is in the organization of the cytoplasmic (C-) loops. The C-II
loop in the β1-adrenergic receptor structure forms a short
α-helix, whereas this loop is more extended in rhodopsin. In addition,
rhodopsin has a native C-III loop that is absent from the
β1-adrenergic receptor structure as a result of deletions
needed for crystallization. C, the structure of the
β1-adrenergic receptor (colored by helix) is displayed with
the human β2-adrenergic receptor (green ribbon) to show the key
structural differences. In this case, the C-II loops of both the
β1- and β2-adrenergic receptors are similar,
but the α-helical conformation of the β1-adrenergic
receptor cannot be accommodated within the two crystallized structures of the
β2-adrenergic receptor because of lattice contacts with
adjacent molecules. D, the structure of the β1-adrenergic
receptor (colored by helix) is displayed with the human A2A
adenosine receptor (green ribbon) to show key structural differences. The main
difference between these two structures lies in the distinct folding of the
extracellular loops, with the adenosine receptor adopting a more open surface
for ligand binding as a result of this folding.