ジャーナル: Structure / 年: 2019 タイトル: Structural and Functional Analyses of the Human PDH Complex Suggest a "Division-of-Labor" Mechanism by Local E1 and E3 Clusters. 著者: Sabin Prajapati / David Haselbach / Sabine Wittig / Mulchand S Patel / Ashwin Chari / Carla Schmidt / Holger Stark / Kai Tittmann / 要旨: The pseudo-atomic structural model of human pyruvate dehydrogenase complex (PDHc) core composed of full-length E2 and E3BP components, calculated from our cryoelectron microscopy-derived density maps ...The pseudo-atomic structural model of human pyruvate dehydrogenase complex (PDHc) core composed of full-length E2 and E3BP components, calculated from our cryoelectron microscopy-derived density maps at 6-Å resolution, is similar to those of prokaryotic E2 structures. The spatial organization of human PDHc components as evidenced by negative-staining electron microscopy and native mass spectrometry is not homogeneous, and entails the unanticipated formation of local clusters of E1:E2 and E3BP:E3 complexes. Such uneven, clustered organization translates into specific duties for E1-E2 clusters (oxidative decarboxylation and acetyl transfer) and E3BP-E3 clusters (regeneration of reduced lipoamide) corresponding to half-reactions of the PDHc catalytic cycle. The addition of substrate coenzyme A modulates the conformational landscape of PDHc, in particular of the lipoyl domains, extending the postulated multiple random coupling mechanism. The conformational and associated chemical landscapes of PDHc are thus not determined entirely stochastically, but are restrained and channeled through an asymmetric architecture and further modulated by substrate binding.
ダウンロード / ファイル: emd_0138.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
ボクセルのサイズ
X=Y=Z: 1.27 Å
密度
表面レベル
登録者による: 0.06 / ムービー #1: 0.06
最小 - 最大
-0.11762706 - 0.29477248
平均 (標準偏差)
0.003969073 (±0.020067863)
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
256
256
256
Spacing
256
256
256
セル
A=B=C: 325.12 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
1.27
1.27
1.27
M x/y/z
256
256
256
origin x/y/z
0.000
0.000
0.000
length x/y/z
325.120
325.120
325.120
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
256
256
256
D min/max/mean
-0.118
0.295
0.004
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添付データ
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試料の構成要素
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全体 : single particle cryo EM-derived map of the full-length native hum...
全体
名称: single particle cryo EM-derived map of the full-length native human E2-E3BP core of the pyruvate dehydrogenase multienzyme complex
要素
複合体: single particle cryo EM-derived map of the full-length native human E2-E3BP core of the pyruvate dehydrogenase multienzyme complex
タンパク質・ペプチド: Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
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超分子 #1: single particle cryo EM-derived map of the full-length native hum...
超分子
名称: single particle cryo EM-derived map of the full-length native human E2-E3BP core of the pyruvate dehydrogenase multienzyme complex タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all
由来(天然)
生物種: Homo sapiens (ヒト)
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分子 #1: Dihydrolipoyllysine-residue acetyltransferase component of pyruva...