National Natural Science Foundation of China (NSFC)
31770796
中国
National Natural Science Foundation of China (NSFC)
81872915
中国
National Natural Science Foundation of China (NSFC)
82073904
中国
National Natural Science Foundation of China (NSFC)
81773792
中国
National Natural Science Foundation of China (NSFC)
81973373
中国
引用
ジャーナル: Nat Struct Mol Biol / 年: 2021 タイトル: Molecular basis for kinin selectivity and activation of the human bradykinin receptors. 著者: Yu-Ling Yin / Chenyu Ye / Fulai Zhou / Jia Wang / Dehua Yang / Wanchao Yin / Ming-Wei Wang / H Eric Xu / Yi Jiang / 要旨: Bradykinin and kallidin are endogenous kinin peptide hormones that belong to the kallikrein-kinin system and are essential to the regulation of blood pressure, inflammation, coagulation and pain ...Bradykinin and kallidin are endogenous kinin peptide hormones that belong to the kallikrein-kinin system and are essential to the regulation of blood pressure, inflammation, coagulation and pain control. Des-Arg-kallidin, the carboxy-terminal des-Arg metabolite of kallidin, and bradykinin selectively activate two G protein-coupled receptors, type 1 and type 2 bradykinin receptors (B1R and B2R), respectively. The hyperactivation of bradykinin receptors, termed 'bradykinin storm', is associated with pulmonary edema in COVID-19 patients, suggesting that bradykinin receptors are important targets for COVID-19 intervention. Here we report two G protein-coupled complex structures of human B1R and B2R bound to des-Arg-kallidin and bradykinin, respectively. Combined with functional analysis, our structures reveal the mechanism of ligand selectivity and specific activation of the bradykinin receptor. These findings also provide a framework for guiding drug design targeting bradykinin receptors for the treatment of inflammation, cardiovascular disorders and COVID-19.
ダウンロード / ファイル: emd_31145.map.gz / 形式: CCP4 / 大きさ: 30.5 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
ボクセルのサイズ
X=Y=Z: 1.08 Å
密度
表面レベル
登録者による: 0.01 / ムービー #1: 0.06
最小 - 最大
-0.017135873 - 1.7136594
平均 (標準偏差)
0.001739553 (±0.02822518)
対称性
空間群: 1
詳細
EMDB XML:
マップ形状
Axis order
X
Y
Z
Origin
0
0
0
サイズ
200
200
200
Spacing
200
200
200
セル
A=B=C: 216.00002 Å α=β=γ: 90.0 °
CCP4マップ ヘッダ情報:
mode
Image stored as Reals
Å/pix. X/Y/Z
1.08
1.08
1.08
M x/y/z
200
200
200
origin x/y/z
0.000
0.000
0.000
length x/y/z
216.000
216.000
216.000
α/β/γ
90.000
90.000
90.000
MAP C/R/S
1
2
3
start NC/NR/NS
0
0
0
NC/NR/NS
200
200
200
D min/max/mean
-0.017
1.714
0.002
-
添付データ
-
試料の構成要素
+
全体 : Cryo-EM structure of the type 1 bradykinin receptor in complex wi...
全体
名称: Cryo-EM structure of the type 1 bradykinin receptor in complex with the des-Arg10-kallidin and an Gq protein
要素
複合体: Cryo-EM structure of the type 1 bradykinin receptor in complex with the des-Arg10-kallidin and an Gq protein
複合体: Type 1 bradykinin receptor
タンパク質・ペプチド: B1 bradykinin receptor
複合体: LYS-ARG-PRO-PRO-GLY-PHE-SER-PRO-PHE
タンパク質・ペプチド: LYS-ARG-PRO-PRO-GLY-PHE-SER-PRO-PHE
複合体: G subunit q (Gi2-mini-Gq chimeric)
タンパク質・ペプチド: G subunit q (Gi1-Gq chimeric)
複合体: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
タンパク質・ペプチド: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
複合体: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
タンパク質・ペプチド: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+
超分子 #1: Cryo-EM structure of the type 1 bradykinin receptor in complex wi...
超分子
名称: Cryo-EM structure of the type 1 bradykinin receptor in complex with the des-Arg10-kallidin and an Gq protein タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all