2G3Q

Solution Structure of Ede1 UBA-ubiquitin complex

Summary for 2G3Q

• Entry DOI: 10.2210/pdb2g3q/pdb
• NMR Information: BMRB: 7002
• Descriptor: Protein YBL047C, Ubiquitin (2 entities in total)
• Functional Keywords: endocytosis, monoubiquitin signaling, solution structure, uba domain, ubiquitin-binding motif, endocytosis-signaling protein complex, endocytosis/signaling protein
• Biological source: Saccharomyces cerevisiae (baker's yeast); More
• Cellular location: Cytoplasm: P34216
• Total number of polymer chains: 2
• Total formula weight: 13255.88

Authors

Swanson, K.A.,Hicke, L.,Radhakrishnan, I. (deposition date: 2006-02-20, release date: 2006-05-09, Last modification date: 2024-05-29)

Primary citation

Swanson, K.A.,Hicke, L.,Radhakrishnan, I.
Structural Basis for Monoubiquitin Recognition by the Ede1 UBA Domain.
J.Mol.Biol., 358:713-724, 2006

PubMed Abstract: Monoubiquitination is a general mechanism for downregulating the activity of cell surface receptors by consigning these proteins for lysosome-mediated degradation through the endocytic pathway. The yeast Ede1 protein functions at the internalization step of endocytosis and binds monoubiquitinated proteins through a ubiquitin associated (UBA) domain. UBA domains are found in a broad range of cellular proteins but previous studies have suggested that the mode of ubiquitin recognition might not be universally conserved. Here we present the solution structure of the Ede1 UBA domain in complex with monoubiquitin. The Ede1 UBA domain forms a three-helix bundle structure and binds ubiquitin through a largely hydrophobic surface in a manner reminiscent of the Dsk2 UBA and the remotely homologous Cue2 CUE domains, for which high-resolution structures have been described. However, the interaction is dissimilar to the molecular models proposed for the hHR23A UBA domains bound to either monoubiquitin or Lys48-linked diubiquitin. Our mutational analyses of the Ede1 UBA domain-ubiquitin interaction reveal several key affinity determinants and, unexpectedly, a negative affinity determinant in the wild-type Ede1 protein, implying that high-affinity interactions may not be the sole criterion for optimal function of monoubiquitin-binding endocytic proteins.

PubMed: 16563434
DOI: 10.1016/j.jmb.2006.02.059

Experimental method

SOLUTION NMR