6DO3

KLHDC2 ubiquitin ligase in complex with SelK C-end degron

Summary for 6DO3

• Entry DOI: 10.2210/pdb6do3/pdb
• Descriptor: Kelch domain-containing protein 2, SelK C-end Degron (3 entities in total)
• Functional Keywords: kelch repeat, beta-propeller, degron, complex, substrate receptor, e3, ubiquitin ligase, ligase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 83953.76

Authors

Rusnac, D.V.,Lin, H.C.,Yen, H.C.S.,Zheng, N. (deposition date: 2018-06-08, release date: 2018-12-19, Last modification date: 2023-10-11)

Primary citation

Rusnac, D.V.,Lin, H.C.,Canzani, D.,Tien, K.X.,Hinds, T.R.,Tsue, A.F.,Bush, M.F.,Yen, H.S.,Zheng, N.
Recognition of the Diglycine C-End Degron by CRL2KLHDC2Ubiquitin Ligase.
Mol. Cell, 72:813-822.e4, 2018

PubMed Abstract: Aberrant proteins can be deleterious to cells and are cleared by the ubiquitin-proteasome system. A group of C-end degrons that are recognized by specific cullin-RING ubiquitin E3 ligases (CRLs) has recently been identified in some of these abnormal polypeptides. Here, we report three crystal structures of a CRL2 substrate receptor, KLHDC2, in complex with the diglycine-ending C-end degrons of two early-terminated selenoproteins and the N-terminal proteolytic fragment of USP1. The E3 recognizes the degron peptides in a similarly coiled conformation and cradles their C-terminal diglycine with a deep surface pocket. By hydrogen bonding with multiple backbone carbonyls of the peptides, KLHDC2 further locks in the otherwise degenerate degrons with a compact interface and unexpected high affinities. Our results reveal the structural mechanism by which KLHDC2 recognizes the simplest C-end degron and suggest a functional necessity of the E3 to tightly maintain the low abundance of its select substrates.

PubMed: 30526872
DOI: 10.1016/j.molcel.2018.10.021

Experimental method

X-RAY DIFFRACTION (2.165 Å)