5X0W

Molecular mechanism for the binding between Sharpin and HOIP

Summary for 5X0W

• Entry DOI: 10.2210/pdb5x0w/pdb
• Descriptor: E3 ubiquitin-protein ligase RNF31, Sharpin (2 entities in total)
• Functional Keywords: sharpin, hoip, linear ubiquitination, e3 enzyme, ligase-protein binding complex, ligase/protein binding
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm : Q96EP0; Cytoplasm, cytosol : Q9H0F6
• Total number of polymer chains: 8
• Total formula weight: 120700.91

Authors

Liu, J.,Li, F.,Cheng, X.,Pan, L. (deposition date: 2017-01-23, release date: 2017-10-18, Last modification date: 2024-11-13)

Primary citation

Liu, J.,Wang, Y.,Gong, Y.,Fu, T.,Hu, S.,Zhou, Z.,Pan, L.
Structural Insights into SHARPIN-Mediated Activation of HOIP for the Linear Ubiquitin Chain Assembly
Cell Rep, 21:27-36, 2017

PubMed Abstract: The linear ubiquitin chain assembly complex (LUBAC) is the sole identified E3 ligase complex that catalyzes the formation of linear ubiquitin chain, and it is composed of HOIP, HOIL-1L, and SHARPIN. The E3 activity of HOIP can be effectively activated by HOIL-1L or SHARPIN, deficiency of which leads to severe immune system disorders. However, the underlying mechanism governing the HOIP-SHARPIN interaction and the SHARPIN-mediated activation of HOIP remains elusive. Here, we biochemically and structurally demonstrate that the UBL domain of SHARPIN specifically binds to the UBA domain of HOIP and thereby associates with and activates HOIP. We further uncover that SHARPIN and HOIL-1L can separately or synergistically bind to distinct sites of HOIP UBA with induced allosteric effects and thereby facilitate the E2 loading of HOIP for its activation. Thus, our findings provide mechanistic insights into the assembly and activation of LUBAC.

PubMed: 28978479
DOI: 10.1016/j.celrep.2017.09.031

Experimental method

X-RAY DIFFRACTION (3 Å)