WT Chicken Scap L1-L7 / Fab 4G10 complex focused refinement
マップデータ
Focused classification map of WT Scap L1-L7/Fab
試料
複合体: Ternary complex of Scap with Fab fragment
複合体: Scap L1-L7 domain
タンパク質・ペプチド: Sterol regulatory element-binding protein cleavage-activating protein
複合体: 4G10 Fab, 4G10 light chain
タンパク質・ペプチド: 4G10 heavy chain
タンパク質・ペプチド: 4G10 light chain
機能・相同性
機能・相同性情報
Regulation of cholesterol biosynthesis by SREBP (SREBF) / SREBP-SCAP complex / regulation of cholesterol biosynthetic process / cellular lipid metabolic process / sterol binding / SREBP signaling pathway / regulation of fatty acid biosynthetic process / positive regulation of cholesterol biosynthetic process / cholesterol metabolic process / response to insulin ...Regulation of cholesterol biosynthesis by SREBP (SREBF) / SREBP-SCAP complex / regulation of cholesterol biosynthetic process / cellular lipid metabolic process / sterol binding / SREBP signaling pathway / regulation of fatty acid biosynthetic process / positive regulation of cholesterol biosynthetic process / cholesterol metabolic process / response to insulin / ER to Golgi transport vesicle membrane / membrane => GO:0016020 / response to hypoxia / immune response / Golgi membrane / endoplasmic reticulum membrane 類似検索 - 分子機能
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35GM116387
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM136976
米国
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)
P01HL020948
米国
Welch Foundation
I-1770
米国
Welch Foundation
I-1793
米国
Welch Foundation
I-1944
米国
Mallinckrodt Foundation
米国
Cancer Prevention and Research Institute of Texas (CPRIT)
RR160082
米国
Leducq Foundation
19CVD04
フランス
American Heart Association
18POST34080141
米国
Cancer Prevention and Research Institute of Texas (CPRIT)
RP170644
米国
引用
ジャーナル: Cell / 年: 2021 タイトル: Scap structures highlight key role for rotation of intertwined luminal loops in cholesterol sensing. 著者: Daniel L Kober / Arun Radhakrishnan / Joseph L Goldstein / Michael S Brown / Lindsay D Clark / Xiao-Chen Bai / Daniel M Rosenbaum / 要旨: The cholesterol-sensing protein Scap induces cholesterol synthesis by transporting membrane-bound transcription factors called sterol regulatory element-binding proteins (SREBPs) from the endoplasmic ...The cholesterol-sensing protein Scap induces cholesterol synthesis by transporting membrane-bound transcription factors called sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum (ER) to the Golgi apparatus for proteolytic activation. Transport requires interaction between Scap's two ER luminal loops (L1 and L7), which flank an intramembrane sterol-sensing domain (SSD). Cholesterol inhibits Scap transport by binding to L1, which triggers Scap's binding to Insig, an ER retention protein. Here we used cryoelectron microscopy (cryo-EM) to elucidate two structures of full-length chicken Scap: (1) a wild-type free of Insigs and (2) mutant Scap bound to chicken Insig without cholesterol. Strikingly, L1 and L7 intertwine tightly to form a globular domain that acts as a luminal platform connecting the SSD to the rest of Scap. In the presence of Insig, this platform undergoes a large rotation accompanied by rearrangement of Scap's transmembrane helices. We postulate that this conformational change halts Scap transport of SREBPs and inhibits cholesterol synthesis.
ダウンロード / ファイル: emd_23405.map.gz / 形式: CCP4 / 大きさ: 75.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
注釈
Focused classification map of WT Scap L1-L7/Fab
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: 0.0537 / ムービー #1: 0.0537
最小 - 最大
-0.20536686 - 0.30715764
平均 (標準偏差)
-5.3366453e-05 (±0.0048753116)
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
270
270
270
Spacing
270
270
270
セル
A=B=C: 291.6 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
270
270
270
origin x/y/z
0.000
0.000
0.000
length x/y/z
291.600
291.600
291.600
α/β/γ
90.000
90.000
90.000
start NX/NY/NZ
192
139
186
NX/NY/NZ
211
274
246
MAP C/R/S
1
2
3
start NC/NR/NS
0
0
0
NC/NR/NS
270
270
270
D min/max/mean
-0.205
0.307
-0.000
-
添付データ
-
試料の構成要素
-
全体 : Ternary complex of Scap with Fab fragment
全体
名称: Ternary complex of Scap with Fab fragment
要素
複合体: Ternary complex of Scap with Fab fragment
複合体: Scap L1-L7 domain
タンパク質・ペプチド: Sterol regulatory element-binding protein cleavage-activating protein
複合体: 4G10 Fab, 4G10 light chain
タンパク質・ペプチド: 4G10 heavy chain
タンパク質・ペプチド: 4G10 light chain
-
超分子 #1: Ternary complex of Scap with Fab fragment
超分子
名称: Ternary complex of Scap with Fab fragment / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: Fab fragment generated by proteolytic cleavage of IgG antibody