TY  - JOUR
AU  - Zhang, Haitao
AU  - Han, Gye Won
AU  - Batyuk, Alexander
AU  - Ishchenko, Andrii
AU  - White, Kate L.
AU  - Patel, Nilkanth
AU  - Sadybekov, Anastasiia
AU  - Zamlynny, Beata
AU  - Rudd, Michael T.
AU  - Hollenstein, Kaspar
AU  - Tolstikova, Alexandra
AU  - White, Thomas A.
AU  - Hunter, Mark S.
AU  - Weierstall, Uwe
AU  - Liu, Wei
AU  - Babaoglu, Kerim
AU  - Moore, Eric L.
AU  - Katz, Ryan D.
AU  - Shipman, Jennifer M.
AU  - Garcia-Calvo, Margarita
AU  - Sharma, Sujata
AU  - Sheth, Payal
AU  - Soisson, Stephen M.
AU  - Stevens, Raymond C.
AU  - Katritch, Vsevolod
AU  - Cherezov, Vadim
TI  - Structural basis for selectivity and diversity in angiotensin II receptors
JO  - Nature 
VL  - 544
IS  - 7650
SN  - 1476-4687
CY  - London [u.a.]
PB  - Nature Publ. Group
M1  - PUBDB-2017-11813
SP  - 327 - 332
PY  - 2017
N1  - © Macmillan Publishers Limited, part of Springer Nature ; Post referee fulltext in progress; Embargo 6 months from publication 
AB  - The angiotensin II receptors AT1R and AT2R serve as key components of the renin–angiotensin–aldosterone system. AT1R has a central role in the regulation of blood pressure, but the function of AT2R is unclear and it has a variety of reported effects. To identify the mechanisms that underlie the differences in function and ligand selectivity between these receptors, here we report crystal structures of human AT2R bound to an AT2R-selective ligand and to an AT1R/AT2R dual ligand, capturing the receptor in an active-like conformation. Unexpectedly, helix VIII was found in a non-canonical position, stabilizing the active-like state, but at the same time preventing the recruitment of G proteins or β-arrestins, in agreement with the lack of signalling responses in standard cellular assays. Structure–activity relationship, docking and mutagenesis studies revealed the crucial interactions for ligand binding and selectivity. Our results thus provide insights into the structural basis of the distinct functions of the angiotensin receptors, and may guide the design of newselective ligands.
LB  - PUB:(DE-HGF)16
C6  - pmid:28379944
UR  - <Go to ISI:>//WOS:000399524400032
DO  - DOI:10.1038/nature22035
UR  - https://bib-pubdb1.desy.de/record/393995
ER  -