{"entry": {"accession": "MF7000867", "general": {"name": "Human FAD-linked augmenter of liver regeneration (ALR)", "pdb_id": "3o55", "exp_method": "X-ray", "resolution": "1.90", "assembly": "Homodimer", "source_organism": "Homo sapiens", "publication": {"pmid": "21383138", "authors": "Banci L, Bertini I, Calderone V, Cefaro C, Ciofi-Baffoni S, Gallo A, Kallergi E, Lionaki E, Pozidis C, Tokatlidis K", "title": "Molecular recognition and substrate mimicry drive the electron-transfer process between MIA40 and ALR.", "journal": "Proc. Natl. Acad. Sci. U.S.A.", "year": "2011", "issue": "12", "volume": "108", "pages": "4811-6", "abstract": "Oxidative protein folding in the mitochondrial intermembrane space requires the transfer of a disulfide bond from MIA40 to the substrate. During this process MIA40 is reduced and regenerated to a functional state through the interaction with the flavin-dependent sulfhydryl oxidase ALR. Here we present the mechanistic basis of ALR-MIA40 interaction at atomic resolution by biochemical and structural analyses of the mitochondrial ALR isoform and its covalent mixed disulfide intermediate with MIA40. This ALR isoform contains a folded FAD-binding domain at the C-terminus and an unstructured, flexible N-terminal domain, weakly and transiently interacting one with the other. A specific region of the N-terminal domain guides the interaction with the MIA40 substrate binding cleft (mimicking the interaction of the substrate itself), without being involved in the import of ALR. The hydrophobicity-driven binding of this region ensures precise protein-protein recognition needed for an efficient electron transfer process."}}, "function": {"molecular_function": {"go": [{"accession": "GO:0050660", "name": "flavin adenine dinucleotide binding"}, {"accession": "GO:0016971", "name": "flavin-dependent sulfhydryl oxidase activity"}, {"accession": "GO:0008083", "name": "growth factor activity"}, {"accession": "GO:0015035", "name": "protein-disulfide reductase activity"}]}, "cellular_component": {"go": [{"accession": "GO:0005829", "name": "cytosol"}, {"accession": "GO:0005615", "name": "extracellular space"}, {"accession": "GO:0005758", "name": "mitochondrial intermembrane space"}, {"accession": "GO:0005739", "name": "mitochondrion"}]}, "biological_process": {"go": [{"accession": "GO:0072717", "name": "cellular response to actinomycin D"}, {"accession": "GO:0071222", "name": "cellular response to lipopolysaccharide"}, {"accession": "GO:0097237", "name": "cellular response to toxic substance"}, {"accession": "GO:0071356", "name": "cellular response to tumor necrosis factor"}, {"accession": "GO:0001889", "name": "liver development"}, {"accession": "GO:0097421", "name": "liver regeneration"}, {"accession": "GO:0043066", "name": "negative regulation of apoptotic process"}, {"accession": "GO:0045953", "name": "negative regulation of natural killer cell mediated cytotoxicity"}, {"accession": "GO:2000573", "name": "positive regulation of DNA biosynthetic process"}]}}, "macromolecules": {"general": {"nr_of_chains": "2", "nr_of_unique_protein_segments": "1", "class": "Homooligomeric enzymes", "subclass": "Homodimeric enzymes", "note": "All chains according to the most probable oligomerization state stored in PDBe were considered."}, "chain": [{"id": "A", "name": "FAD-linked sulfhydryl oxidase ALR", "source_organism": "Homo sapiens", "uniprot": {"id": "P55789", "start": "91", "end": "205", "coverage": "56%", "sequence": "MAAPGERGRFHGGNLFFLPGGARSEMMDDLATDARGRGAGRRDAAASASTPAQAPTSDSPVAEDASRRRPCRACVDFKTWMRTQQKRDTKFREDCPPDREELGRHSWAVLHTLAAYYPDLPTPEQQQDMAQFIHLFSKFYPCEECAEDLRKRLCRNHPDTRTRACFTQWLCHLHNEVNRKLGKPDFDCSKVDERWRDGWKDGSCD", "length": "205"}, "regions": {"region": [{"region_type": "secondary structure", "region_name": "helix", "region_start": "18", "region_end": "36"}, {"region_type": "secondary structure", "region_name": "helix", "region_start": "42", "region_end": "60"}, {"region_type": "secondary structure", "region_name": "helix", "region_start": "62", "region_end": "76"}, {"region_type": "secondary structure", "region_name": "helix", "region_start": "82", "region_end": "101"}, {"region_type": "secondary structure", "region_name": "helix", "region_start": "107", "region_end": "109"}, {"region_type": "secondary structure", "region_name": "helix", "region_start": "110", "region_end": "116"}, {"region_type": "pfam", "region_id": "PF04777", "region_name": "Erv1 / Alr family", "region_start": "104", "region_end": "196"}]}}, {"id": "A-2", "name": "FAD-linked sulfhydryl oxidase ALR", "source_organism": "Homo sapiens", "uniprot": {"id": "P55789", "start": "91", "end": "205", "coverage": "56%", "sequence": "MAAPGERGRFHGGNLFFLPGGARSEMMDDLATDARGRGAGRRDAAASASTPAQAPTSDSPVAEDASRRRPCRACVDFKTWMRTQQKRDTKFREDCPPDREELGRHSWAVLHTLAAYYPDLPTPEQQQDMAQFIHLFSKFYPCEECAEDLRKRLCRNHPDTRTRACFTQWLCHLHNEVNRKLGKPDFDCSKVDERWRDGWKDGSCD", "length": "205"}, "regions": {"region": {"region_type": "pfam", "region_id": "PF04777", "region_name": "Erv1 / Alr family", "region_start": "104", "region_end": "196"}}}]}, "evidence": {"evidence_level": "Insufficient evidence (candidate)", "evidence_coverage": "The full structure participates in mutual synergistic folding.", "sequence_domain": "ERV/ALR sulfhydryl oxidase domain", "complex_evidence": "There is no information on the stability/disorder of the monomeric forms of FAD-linked sulfhydryl oxidases. The wild-type protein is a dimer in solution (analytical equilibrium ultracentrifugation) (PMID:19576902). The, large, hydrophobic interface is made up of two longer, nearly antiparallel helices per monomer that mediate helix packing interactions to form the interface.", "chain_evidence": [{"chain_id": "A", "support": "N/A"}, {"chain_id": "A-2", "support": "N/A"}]}, "related_structures": {"id": ["MF7000866", "MF7000270", "MF7000867", "MF7000868", "MF7000869", "MF7000870"]}}}