التفاصيل البيبلوغرافية
| العنوان: |
E2-RING Expansion of the NEDD8 Cascade Confers Specificity to Cullin Modification |
| المؤلفون: |
Huang, Danny T.1,2, Ayrault, Olivier2, Hunt, Harold W.1, Taherbhoy, Asad M.1,3, Duda, David M.1,4, Scott, Daniel C.1,4, Borg, Laura A.1, Neale, Geoffrey5, Murray, Peter J.6, Roussel, Martine F.2,3 martine.roussel@stjude.org, Schulman, Brenda A.1,2,3,7 brenda.schulman@stjude.org |
| المصدر: |
Molecular Cell. Feb2009, Vol. 33 Issue 4, p483-495. 13p. |
| مصطلحات موضوعية: |
*UBIQUITIN, *RING formation (Chemistry), *LIGASES, *STRUCTURAL analysis (Science), *IMMUNOSPECIFICITY, *HYDROPHOBIC surfaces |
| مستخلص: |
Summary: Ubiquitin and ubiquitin-like proteins (UBLs) are directed to targets by cascades of E1, E2, and E3 enzymes. The largest ubiquitin E3 subclass consists of cullin-RING ligases (CRLs), which contain one each of several cullins (CUL1, -2, -3, -4, or -5) and RING proteins (RBX1 or -2). CRLs are activated by ligation of the UBL NEDD8 to a conserved cullin lysine. How is cullin NEDD8ylation specificity established? Here we report that, like UBE2M (also known as UBC12), the previously uncharacterized E2 UBE2F is a NEDD8-conjugating enzyme in vitro and in vivo. Biochemical and structural analyses indicate how plasticity of hydrophobic E1-E2 interactions and E1 conformational flexibility allow one E1 to charge multiple E2s. The E2s have distinct functions, with UBE2M/RBX1 and UBE2F/RBX2 displaying different target cullin specificities. Together, these studies reveal the molecular basis for and functional importance of hierarchical expansion of the NEDD8 conjugation system in establishing selective CRL activation. [Copyright &y& Elsevier] |
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