3PT3

Structure of the HECT C-lobe of the UBR5 E3 ubiquitin ligase.

(2012) Acta Crystallogr Sect F Struct Biol Cryst Commun 68: 1158-1163

• PubMed: 23027739 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1107/S1744309112036937
• Primary Citation of Related Structures:  
  3PT3


• PubMed Abstract: 
  

  UBR5 ubiquitin ligase (also known as EDD, Rat100 or hHYD) is a member of the E3 protein family of HECT (homologous to E6-AP C-terminus) ligases as it contains a C-terminal HECT domain. In ubiquitination cascades involving E3s of the HECT class, ubiquitin is transferred from an associated E2 ubiquitin-conjugating enzyme to the acceptor cysteine of the HECT domain, which consists of structurally distinct N- and C-lobes connected by a flexible linker. Here, the high-resolution crystal structure of the C-lobe of the HECT domain of human UBR5 is presented. The structure reveals important features that are unique compared with other HECT domains. In particular, a distinct four-residue insert in the second helix elongates this helix, resulting in a strikingly different orientation of the preceding loop. This protruding loop is likely to contribute to specificity towards the E2 ubiquitin-conjugating enzyme UBCH4, which is an important functional partner of UBR5. Ubiquitination assays showed that the C-lobe of UBR5 is able to form a thioester-linked E3-ubiquitin complex, although it does not physically interact with UBCH4 in NMR experiments. This study contributes to a better understanding of UBR5 ubiquitination activity.

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Organizational Affiliation: 

Groupe de Recherche axé sur la Structure des Protéines, Department of Biochemistry, McGill University, Montreal, Quebec H3G 0B1, Canada.