Coordination of Hpr1 and Ubiquitin Binding by the UBA Domain of the mRNA Export Factor Mex67. - Inria - Institut national de recherche en sciences et technologies du numérique Accéder directement au contenu
Article Dans Une Revue Molecular Biology of the Cell Année : 2007

Coordination of Hpr1 and Ubiquitin Binding by the UBA Domain of the mRNA Export Factor Mex67.

Résumé

Monitoring Editor: Thomas Sommer The ubiquitin-associated (UBA) domain of the mRNA nuclear export receptor Mex67 helps coordinating transcription elongation and nuclear export by interacting both with ubiquitin conjugates and specific targets, such as Hpr1, a component of the THO complex. Here we analyzed substrate specificity and ubiquitin selectivity of the Mex67 UBA domain. UBA-Mex67 is formed by three helices arranged in a classical UBA fold plus a fourth helix, H4. Deletion or mutation of helix H4 strengthens the interaction between UBA-Mex67 and ubiquitin, but decreases its affinity for Hpr1. Interaction with Hpr1 is required for Mex67 UBA domain to bind poly-ubiquitin, possibly by inducing an H4-dependent conformational change. In vivo, deletion of helix H4 reduces cotranscriptional recruitment of Mex67 on activated genes and also shows a mRNA export defect. Based on these results, we propose that H4 functions as a molecular switch that coordinates the interaction of Mex67 with ubiquitin bound to specific substrates, defines the selectivity of the Mex67 UBA domain for poly-ubiquitin and prevents its binding to nonspecific substrates.

Dates et versions

hal-00151951 , version 1 (05-06-2007)

Identifiants

Citer

Maria Hobeika, Christoph Brockmann, Nahid Iglesias, Carole Gwizdek, David Neuhaus, et al.. Coordination of Hpr1 and Ubiquitin Binding by the UBA Domain of the mRNA Export Factor Mex67.. Molecular Biology of the Cell, 2007, 18 (7), pp.2561-2568. ⟨10.1091/mbc.E07-02-0153⟩. ⟨hal-00151951⟩
91 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More