ubiquitinbinding

Ubiquitin binding is the recognition of ubiquitin by non-enzymatic factors, most commonly proteins that contain ubiquitin-binding domains (UBDs) or ubiquitin-interacting motifs. Ubiquitin is a small regulatory protein that can be covalently attached to substrates and to other ubiquitin molecules to form polyubiquitin chains with different linkages, affecting stability, localization, or activity of the substrate. Ubiquitin-binding proteins can recognize mono-ubiquitin or specific polyubiquitin chain architectures, enabling a range of cellular processes.

Common ubiquitin-binding modules include UBA (ubiquitin-associated), UIM (ubiquitin-interacting motif), NZF (Npl4 zinc finger), UBM, and CUE; many proteins carry tandem repeats that confer higher affinity or linkage preference. The binding interface often centers on the Ile44 hydrophobic patch on ubiquitin and may involve complementary surfaces on the Ub-binding domain. Linkage type (e.g., K48- vs K63-linked chains) and chain length influence recognition and downstream outcomes.

Biological roles: In proteasomal degradation, receptors such as Rpn10 and Rpn13 recognize polyubiquitinated substrates; in autophagy, receptors like p62 and NBR1 bind Ub chains via UBA domains and link to LC3 membranes; in signaling and DNA repair, Ub-binding factors modulate assembly of signaling complexes and repair foci. Deubiquitinases also engage ubiquitin via Ub-binding sites to edit chains.

Regulation and significance: Ub-binding is dynamic and competitive; alterations in Ub-binding can disrupt proteostasis and have been implicated in neurodegenerative diseases and cancer. Research continues to map Ub-binding networks and their impact on cellular pathways.