6CDG

GID4 fragment in complex with a peptide

Summary for 6CDG

• Entry DOI: 10.2210/pdb6cdg/pdb
• Descriptor: Glucose-induced degradation protein 4 homolog, Hexapeptide PGLWKS, UNKNOWN ATOM OR ION, ... (4 entities in total)
• Functional Keywords: structural genomics consortium, sgc, peptide binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 20292.58

Authors

Dong, C.,Tempel, W.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.M.,Min, J.,Structural Genomics Consortium (SGC) (deposition date: 2018-02-08, release date: 2018-03-07, Last modification date: 2024-04-03)

Primary citation

Dong, C.,Zhang, H.,Li, L.,Tempel, W.,Loppnau, P.,Min, J.
Molecular basis of GID4-mediated recognition of degrons for the Pro/N-end rule pathway.
Nat. Chem. Biol., 14:466-473, 2018

PubMed Abstract: The N-end rule pathway senses the N-terminal destabilizing residues of degradation substrates for the ubiquitin-proteasome system, whose integrity shields against various human syndromes including cancer and cardiovascular diseases. GID4, a subunit of the ubiquitin ligase GID complex, has been recently identified as the N-recognin of the new branch of the N-end rule pathway responsible for recognizing substrates bearing N-terminal proline residues (Pro/N-degrons). However, the molecular mechanism of GID4-mediated Pro/N-degron recognition remains largely unexplored. Here, we report the first crystal structures of human GID4 alone and in complex with various Pro/N-degrons. Our complex crystal structures, together with biophysical analyses, delineate the GID4-mediated Pro/N-degron recognition mechanism and substrate selection criteria for the Pro/N-end rule pathway. These mechanistic data on the Pro/N-recognin activity of GID4 will serve as a foundation to facilitate the identification of authentic physiological substrates as well as the development of inhibitors of therapeutic values for the Pro/N-end rule pathway.

PubMed: 29632410
DOI: 10.1038/s41589-018-0036-1

Experimental method

X-RAY DIFFRACTION (1.6 Å)