ジャーナル: Nat Commun / 年: 2022 タイトル: Structural basis of neuropeptide Y signaling through Y1 receptor. 著者: Chaehee Park / Jinuk Kim / Seung-Bum Ko / Yeol Kyo Choi / Hyeongseop Jeong / Hyeonuk Woo / Hyunook Kang / Injin Bang / Sang Ah Kim / Tae-Young Yoon / Chaok Seok / Wonpil Im / Hee-Jung Choi / 要旨: Neuropeptide Y (NPY) is highly abundant in the brain and involved in various physiological processes related to food intake and anxiety, as well as human diseases such as obesity and cancer. However, ...Neuropeptide Y (NPY) is highly abundant in the brain and involved in various physiological processes related to food intake and anxiety, as well as human diseases such as obesity and cancer. However, the molecular details of the interactions between NPY and its receptors are poorly understood. Here, we report a cryo-electron microscopy structure of the NPY-bound neuropeptide Y1 receptor (YR) in complex with G protein. The NPY C-terminal segment forming the extended conformation binds deep into the YR transmembrane core, where the amidated C-terminal residue Y36 of NPY is located at the base of the ligand-binding pocket. Furthermore, the helical region and two N-terminal residues of NPY interact with YR extracellular loops, contributing to the high affinity of NPY for YR. The structural analysis of NPY-bound YR and mutagenesis studies provide molecular insights into the activation mechanism of YR upon NPY binding.
Last 11 residues (AAAHHHHHHHH) of chain S are expression tags.
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実験情報
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実験
実験
手法: 電子顕微鏡法
EM実験
試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法
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試料調製
構成要素
ID
名称
タイプ
Entity ID
Parent-ID
由来
1
Complex of Neuropeptide Y Y1 Receptor (NPY1R) with its endogeneous Peptide-Agonist Neuropeptide Y (NPY), G Protein and G-protein stabilizing antibody fragement (scFv16)
COMPLEX
all
0
MULTIPLESOURCES
2
NeuropeptideYY1Receptor (NPY1R)
COMPLEX
#1
1
RECOMBINANT
3
nucleotide-free G-Protein heterotrimer
COMPLEX
#3-#5
1
RECOMBINANT
4
NeuropeptideY
COMPLEX
#2
1
SYNTHETIC
5
single-chain antibody Fv fragment (scFv16)
COMPLEX
#6
1
RECOMBINANT
分子量
値: 0.16 MDa / 実験値: NO
由来(天然)
ID
Entity assembly-ID
生物種
Ncbi tax-ID
2
2
Homo sapiens (ヒト)
9606
3
3
Homo sapiens (ヒト)
9606
5
5
Mus musculus (ハツカネズミ)
10090
由来(組換発現)
ID
Entity assembly-ID
生物種
Ncbi tax-ID
2
2
Spodoptera frugiperda (ツマジロクサヨトウ)
7108
3
3
Spodoptera frugiperda (ツマジロクサヨトウ)
7108
4
3
Escherichia coli (大腸菌)
562
5
5
Trichoplusia ni (イラクサキンウワバ)
7111
緩衝液
pH: 8
緩衝液成分
ID
濃度
名称
式
Buffer-ID
1
20mM
hydroxyethylpiperazineethanesulfonicacid
HEPES
1
2
150mM
sodiumchloride
NaCl
1
3
0.01 %
glyco-diosgenin
GDN
1
試料
濃度: 10 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES