8BVL

Crystal structure of the IBR-RING2 domain of HOIL-1

Summary for 8BVL

• Entry DOI: 10.2210/pdb8bvl/pdb
• Descriptor: RanBP-type and C3HC4-type zinc finger-containing protein 1, ZINC ION (3 entities in total)
• Functional Keywords: lubac, ubiquitin, rbck1, hoip, sharpin, rbr ligase, e3 ligase, ligase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 33325.73

Authors

Stieglitz, B.,Koliopoulos, M.G.,Rittinger, K. (deposition date: 2022-12-04, release date: 2023-01-18, Last modification date: 2024-06-19)

Primary citation

Wu, Q.,Koliopoulos, M.G.,Rittinger, K.,Stieglitz, B.
Structural basis for ubiquitylation by HOIL-1.
Front Mol Biosci, 9:1098144-1098144, 2022

PubMed Abstract: The linear ubiquitin chain assembly complex synthesises linear Ub chains which constitute a binding and activation platform for components of the TNF signalling pathway. One of the components of LUBAC is the ubiquitin ligase HOIL-1 which has been shown to generate oxyester linkages on several proteins and on linear polysaccharides. We show that HOIL-1 activity requires linear tetra-Ub binding which enables HOIL-1 to mono-ubiquitylate linear Ub chains and polysaccharides. Furthermore, we describe the crystal structure of a C-terminal tandem domain construct of HOIL-1 comprising the IBR and RING2 domains. Interestingly, the structure reveals a unique bi-nuclear Zn-cluster which substitutes the second zinc finger of the canonical RING2 fold. We identify the C-terminal histidine of this bi-nuclear Zn-cluster as the catalytic base required for the ubiquitylation activity of HOIL-1. Our study suggests that the unique zinc-coordinating architecture of RING2 provides a binding platform for ubiquitylation targets.

PubMed: 36685275
DOI: 10.3389/fmolb.2022.1098144

Experimental method

X-RAY DIFFRACTION (2.24 Å)