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Insights into Ubiauitin Transfer Cascades from a Structure of a UbcH5B similar to Ubiauitin-HECTNEDD4L Complex
Journal article   Open access   Peer reviewed

Insights into Ubiauitin Transfer Cascades from a Structure of a UbcH5B similar to Ubiauitin-HECTNEDD4L Complex

Hari B. Kamadurai, Judith Souphron, Daniel C. Scott, David M. Duda, Darcie J. Miller, Daniel Stringer, Robert C. Piper and Brenda A. Schulman
Molecular cell, Vol.36(6), pp.1095-1102
12/24/2009
DOI: 10.1016/j.molcel.2009.11.010
PMCID: PMC2859195
PMID: 20064473
url
https://doi.org/10.1016/j.molcel.2009.11.010View
Published (Version of record) Open Access

Abstract

In E1-E2-E3 ubiquitin (Ub) conjugation cascades, the E2 first forms a transient E2 similar to Ub covalent complex and then interacts with an E3 for Ub transfer. For cascades involving E3s in the HECT class, Ub is transferred from an associated E2 to the acceptor cysteine in the HECT domain C lobe. To gain insights into this process, we determined the crystal structure of a complex between the HECT domain of NEDD4L and the E2 UbcH5B bearing a covalently linked Ub at its active site (UbcH5B similar to Ub). Noncovalent interactions between UbcH5B and the HECT N lobe and between Ub and the HECT domain C lobe lead to an overall compact structure, with the Ub C terminus sandwiched between UbcH5B and HECT domain active sites. The structure suggests a model for E2-to-HECT Ub transfer, in which interactions between a donor Ub and an acceptor domain constrain upstream and downstream enzymes for conjugation.
Biochemistry & Molecular Biology Cell Biology Life Sciences & Biomedicine Science & Technology

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