2. Academic Validation
  3. The intrinsic affinity between E2 and the Cys domain of E1 in ubiquitin-like modifications

The intrinsic affinity between E2 and the Cys domain of E1 in ubiquitin-like modifications

  • Mol Cell. 2007 Jul 20;27(2):228-237. doi: 10.1016/j.molcel.2007.05.023.
Jianghai Wang 1,  Weidong Hu 1,  Sheng Cai 1,  Brian Lee 2,  Jing Song 3,  Yuan Chen 4
Affiliations

Affiliations

  • 1 Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
  • 2 Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA; City of Hope Summer Internship Program, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA; Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
  • 3 Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA; City of Hope Graduate School, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
  • 4 Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA. Electronic address: ychen@coh.org.
PMID: 17643372 DOI: 10.1016/j.molcel.2007.05.023
Abstract

Ubiquitin-like modifications, which are carried out by similar biochemical mechanisms, regulate nearly every aspect of cellular function. Despite the recent advancements in characterizing their enzymology, our knowledge about the dynamic processes of these modifications is still fragmentary. In this study, we have uncovered an intrinsic affinity between the SUMO E2 and the Cys domain of SUMO E1. NMR studies in combination with paramagnetic spin labeling demonstrate that this interaction is mediated by previously unknown interfaces on both E1 and E2 and places the two catalytic Cys residues of the two Enzymes in close proximity. Site-directed mutagenesis and enzymatic assays indicate that the interaction is fundamentally important for the transfer of SUMO from E1 to E2. Results from this study suggest that the interaction between E2 and the Cys domain of E1 participates in guiding the E2's translocation to E1's enzymatic active site in ubiquitin-like modifications.

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