4XKH

CRYSTAL STRUCTURE OF THE AIRAPL TANDEM UIMS IN COMPLEX WITH A LYS48-LINKED TRI-UBIQUITIN

Summary for 4XKH

• Entry DOI: 10.2210/pdb4xkh/pdb
• Descriptor: Polyubiquitin-C, AN1-type zinc finger protein 2B (3 entities in total)
• Functional Keywords: tandem ubiquitin-interacting motifs, ubiquitin-binding, ubiquitin-binding protein
• Biological source: Bos taurus (Bovine); More
• Cellular location: Cytoplasm : P0CH28; Endoplasmic reticulum: Q91X58
• Total number of polymer chains: 9
• Total formula weight: 68861.78

Authors

Rahighi, S.,Kawasaki, M.,Stanhill, A.,Wakatsuki, S. (deposition date: 2015-01-11, release date: 2016-02-17, Last modification date: 2024-02-28)

Primary citation

Rahighi, S.,Braunstein, I.,Ternette, N.,Kessler, B.,Kawasaki, M.,Kato, R.,Matsui, T.,Weiss, T.M.,Stanhill, A.,Wakatsuki, S.
Selective Binding of AIRAPL Tandem UIMs to Lys48-Linked Tri-Ubiquitin Chains.
Structure, 24:412-422, 2016

PubMed Abstract: Lys48-linked ubiquitin chains act as the main targeting signals for protein degradation by the proteasome. Here we report selective binding of AIRAPL, a protein that associates with the proteasome upon exposure to arsenite, to Lys48-linked tri-ubiquitin chains. AIRAPL comprises two ubiquitin-interacting motifs in tandem (tUIMs) that are linked through a flexible inter-UIM region. In the complex crystal structure UIM1 binds the proximal ubiquitin, whereas UIM2 (the double-sided UIM) binds non-symmetrically to the middle and distal ubiquitin moieties on either side of the helix. Specificity of AIRAPL for Lys48-linked ubiquitin chains is determined by UIM2, and the flexible inter-UIM linker increases avidity by placing the two UIMs in an orientation that facilitates binding of the third ubiquitin to UIM1. Unlike middle and proximal ubiquitins, distal ubiquitin binds UIM2 through a novel surface, which leaves the Ile44 hydrophobic patch accessible for binding to the proteasomal ubiquitin receptors.

PubMed: 26876100
DOI: 10.1016/j.str.2015.12.017

Experimental method

X-RAY DIFFRACTION (3 Å)