2CY7

The crystal structure of human Atg4B

Summary for 2CY7

• Entry DOI: 10.2210/pdb2cy7/pdb
• Descriptor: Cysteine protease APG4B (2 entities in total)
• Functional Keywords: papain-like fold, autophagy, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (Probable): Q9Y4P1
• Total number of polymer chains: 1
• Total formula weight: 44645.49

Authors

Sugawara, K.,Suzuki, N.N.,Fujioka, Y.,Mizushima, N.,Ohsumi, Y.,Inagaki, F. (deposition date: 2005-07-05, release date: 2005-09-13, Last modification date: 2024-03-13)

Primary citation

Sugawara, K.,Suzuki, N.N.,Fujioka, Y.,Mizushima, N.,Ohsumi, Y.,Inagaki, F.
Structural Basis for the Specificity and Catalysis of Human Atg4B Responsible for Mammalian Autophagy
J.Biol.Chem., 280:40058-40065, 2005

PubMed Abstract: Reversible modification of Atg8 with phosphatidylethanolamine is crucial for autophagy, the bulk degradation system conserved in eukaryotic cells. Atg4 is a novel cysteine protease that processes and deconjugates Atg8. Herein, we report the crystal structure of human Atg4B (HsAtg4B) at 1.9-A resolution. Despite no obvious sequence homology with known proteases, the structure of HsAtg4B shows a classical papain-like fold. In addition to the papain fold region, HsAtg4B has a small alpha/beta-fold domain. This domain is thought to be the binding site for Atg8 homologs. The active site cleft of HsAtg4B is masked by a loop (residues 259-262), implying a conformational change upon substrate binding. The structure and in vitro mutational analyses provide the basis for the specificity and catalysis of HsAtg4B. This will enable the design of Atg4-specific inhibitors that block autophagy.

PubMed: 16183633
DOI: 10.1074/jbc.M509158200

Experimental method

X-RAY DIFFRACTION (1.9 Å)