UNIGE document Scientific Article
previous document  unige:13226  next document
add to browser collection
Title

Coordination of Hpr1 and ubiquitin binding by the UBA domain of the mRNA export factor Mex67

Authors
Hobeika, Maria
Brockmann, Christoph
Gwizdek, Carole
Neuhaus, David
Stewart, Murray
Divita, Gilles
show hidden authors show all authors [1 - 9]
Published in Molecular Biology of the Cell. 2007, vol. 18, no. 7, p. 2561-8
Abstract The ubiquitin-associated (UBA) domain of the mRNA nuclear export receptor Mex67 helps in 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 it decreases its affinity for Hpr1. Interaction with Hpr1 is required for Mex67 UBA domain to bind polyubiquitin, possibly by inducing an H4-dependent conformational change. In vivo, deletion of helix H4 reduces cotranscriptional recruitment of Mex67 on activated genes, and it also shows an 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 polyubiquitin, and prevents its binding to nonspecific substrates.
Keywords Active Transport, Cell NucleusCell Nucleus/metabolismKineticsNuclear Magnetic Resonance, BiomolecularNuclear Proteins/chemistry/genetics/metabolismNucleocytoplasmic Transport Proteins/chemistry/genetics/metabolismProtein BindingProtein Structure, SecondaryProtein Structure, TertiaryProtein TransportRNA TransportRNA, Messenger/genetics/metabolismRNA-Binding Proteins/chemistry/genetics/metabolismSaccharomyces cerevisiae/cytology/metabolismSaccharomyces cerevisiae Proteins/chemistry/genetics/metabolismSequence DeletionSolutionsSurface Plasmon ResonanceTranscription, GeneticUbiquitin/metabolism
Stable URL http://archive-ouverte.unige.ch/unige:13226
Full text
Article (Published version) (755 Kb) - public document Free access
Identifiers
PMID: 17475778
Structures

178 hits

140 downloads

Update

Deposited on : 2011-01-21

Export document
Format :
Citation style :