2cy7
From Proteopedia
The crystal structure of human Atg4B
Structural highlights
Function[ATG4B_HUMAN] Cysteine protease required for autophagy, which cleaves the C-terminal part of MAP1LC3, GABARAPL1, GABARAPL2 and GABARAP, allowing the liberation of form I. A subpopulation of form I is subsequently converted to a smaller form (form II). Form II, with a revealed C-terminal glycine, is considered to be the phosphatidylethanolamine (PE)-conjugated form, and has the capacity for the binding to autophagosomes. Also mediates the lipid deconjugation required for target recycling.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedReversible 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. Structural basis for the specificity and catalysis of human Atg4B responsible for mammalian autophagy.,Sugawara K, Suzuki NN, Fujioka Y, Mizushima N, Ohsumi Y, Inagaki F J Biol Chem. 2005 Dec 2;280(48):40058-65. Epub 2005 Sep 23. PMID:16183633[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Large Structures | Fujioka, Y | Inagaki, F | Mizushima, N | Ohsumi, Y | Sugawara, K | Suzuki, N N | Autophagy | Hydrolase | Papain-like fold
