Molecular basis for the association of human E4B U box ubiquitin ligase with E2-conjugating enzymes UbcH5c and Ubc4

Robert C. Benirschke, James R. Thompson, Yves Nominé, Emeric Wasielewski, Nenad Juranić, Slobodan Macura, Shigetsugu Hatakeyama, Keiichi I. Nakayama, Maria Victoria Botuyan, Georges Mer

研究成果: ジャーナルへの寄稿記事

26 引用 (Scopus)

抄録

Human E4B, also called UFD2a, is a U box-containing protein that functions as an E3 ubiquitin ligase and an E4 polyubiquitin chain elongation factor. E4B is thought to participate in the proteasomal degradation of misfolded or damaged proteins through association with chaperones. The U box domain is an anchor site for E2 ubiquitin-conjugating enzymes, but little is known of the binding mechanism. Using X-ray crystallography and NMR spectroscopy, we determined the structures of E4B U box free and bound to UbcH5c and Ubc4 E2s. Whereas previously characterized U box domains are homodimeric, we show that E4B U box is a monomer stabilized by a network of hydrogen bonds identified from scalar coupling measurements. These structural studies, complemented by calorimetry- and NMR-based binding assays, suggest an allosteric regulation of UbcH5c and Ubc4 by E4B U box and provide a molecular basis to understand how the ubiquitylation machinery involving E4B assembles.

元の言語英語
ページ(範囲)955-965
ページ数11
ジャーナルStructure
18
発行部数8
DOI
出版物ステータス出版済み - 8 1 2010

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Ligases
Ubiquitin
Polyubiquitin
Allosteric Regulation
Ubiquitin-Conjugating Enzymes
Peptide Elongation Factors
Calorimetry
Ubiquitin-Protein Ligases
Ubiquitination
X Ray Crystallography
Enzymes
Hydrogen
Proteins
Magnetic Resonance Spectroscopy

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

これを引用

Benirschke, R. C., Thompson, J. R., Nominé, Y., Wasielewski, E., Juranić, N., Macura, S., ... Mer, G. (2010). Molecular basis for the association of human E4B U box ubiquitin ligase with E2-conjugating enzymes UbcH5c and Ubc4. Structure, 18(8), 955-965. https://doi.org/10.1016/j.str.2010.04.017

Molecular basis for the association of human E4B U box ubiquitin ligase with E2-conjugating enzymes UbcH5c and Ubc4. / Benirschke, Robert C.; Thompson, James R.; Nominé, Yves; Wasielewski, Emeric; Juranić, Nenad; Macura, Slobodan; Hatakeyama, Shigetsugu; Nakayama, Keiichi I.; Botuyan, Maria Victoria; Mer, Georges.

:: Structure, 巻 18, 番号 8, 01.08.2010, p. 955-965.

研究成果: ジャーナルへの寄稿記事

Benirschke, RC, Thompson, JR, Nominé, Y, Wasielewski, E, Juranić, N, Macura, S, Hatakeyama, S, Nakayama, KI, Botuyan, MV & Mer, G 2010, 'Molecular basis for the association of human E4B U box ubiquitin ligase with E2-conjugating enzymes UbcH5c and Ubc4', Structure, 巻. 18, 番号 8, pp. 955-965. https://doi.org/10.1016/j.str.2010.04.017
Benirschke RC, Thompson JR, Nominé Y, Wasielewski E, Juranić N, Macura S その他. Molecular basis for the association of human E4B U box ubiquitin ligase with E2-conjugating enzymes UbcH5c and Ubc4. Structure. 2010 8 1;18(8):955-965. https://doi.org/10.1016/j.str.2010.04.017
Benirschke, Robert C. ; Thompson, James R. ; Nominé, Yves ; Wasielewski, Emeric ; Juranić, Nenad ; Macura, Slobodan ; Hatakeyama, Shigetsugu ; Nakayama, Keiichi I. ; Botuyan, Maria Victoria ; Mer, Georges. / Molecular basis for the association of human E4B U box ubiquitin ligase with E2-conjugating enzymes UbcH5c and Ubc4. :: Structure. 2010 ; 巻 18, 番号 8. pp. 955-965.
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