7Q50

human Gid4 bound to a Phe/N-peptide

Summary for 7Q50

• Entry DOI: 10.2210/pdb7q50/pdb
• Related: 7Q4Y
• Descriptor: Glucose-induced degradation protein 4 homolog, FDVSWFMG peptide (3 entities in total)
• Functional Keywords: gid, ctlh, ubiquitin, e3 ligase, ligase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 20965.40

Authors

Chrustowicz, J.,Sherpa, D.,Loke, M.S.,Prabu, J.R.,Schulman, B.A. (deposition date: 2021-11-02, release date: 2022-03-02, Last modification date: 2024-01-31)

Primary citation

Chrustowicz, J.,Sherpa, D.,Teyra, J.,Loke, M.S.,Popowicz, G.M.,Basquin, J.,Sattler, M.,Prabu, J.R.,Sidhu, S.S.,Schulman, B.A.
Multifaceted N-Degron Recognition and Ubiquitylation by GID/CTLH E3 Ligases.
J.Mol.Biol., 434:167347-167347, 2022

PubMed Abstract: N-degron E3 ubiquitin ligases recognize specific residues at the N-termini of substrates. Although molecular details of N-degron recognition are known for several E3 ligases, the range of N-terminal motifs that can bind a given E3 substrate binding domain remains unclear. Here, we discovered capacity of Gid4 and Gid10 substrate receptor subunits of yeast "GID"/human "CTLH" multiprotein E3 ligases to tightly bind a wide range of N-terminal residues whose recognition is determined in part by the downstream sequence context. Screening of phage displaying peptide libraries with exposed N-termini identified novel consensus motifs with non-Pro N-terminal residues binding Gid4 or Gid10 with high affinity. Structural data reveal that conformations of flexible loops in Gid4 and Gid10 complement sequences and folds of interacting peptides. Together with analysis of endogenous substrate degrons, the data show that degron identity, substrate domains harboring targeted lysines, and varying E3 ligase higher-order assemblies combinatorially determine efficiency of ubiquitylation and degradation.

PubMed: 34767800
DOI: 10.1016/j.jmb.2021.167347

Experimental method

X-RAY DIFFRACTION (3.16 Å)