Database accession: MF7000867
Name: Human FAD-linked augmenter of liver regeneration (ALR)
PDB ID: 3o55
Experimental method: X-ray (1.90 Å)
Assembly: Homodimer
Source organism: Homo sapiens
Primary publication of the structure:
Banci L, Bertini I, Calderone V, Cefaro C, Ciofi-Baffoni S, Gallo A, Kallergi E, Lionaki E, Pozidis C, Tokatlidis K
Molecular recognition and substrate mimicry drive the electron-transfer process between MIA40 and ALR.
(2011) Proc. Natl. Acad. Sci. U.S.A. 108: 4811-6
PMID: 21383138
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.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
flavin adenine dinucleotide binding flavin adenine dinucleotide binding
flavin-dependent sulfhydryl oxidase activity flavin-dependent sulfhydryl oxidase activity
growth factor activity growth factor activity
protein-disulfide reductase activity protein-disulfide reductase activity
Biological process:
cellular response to actinomycin D cellular response to actinomycin D
cellular response to lipopolysaccharide cellular response to lipopolysaccharide
cellular response to toxic substance cellular response to toxic substance
cellular response to tumor necrosis factor cellular response to tumor necrosis factor
liver development liver development
liver regeneration liver regeneration
negative regulation of apoptotic process negative regulation of apoptotic process
negative regulation of natural killer cell mediated cytotoxicity negative regulation of natural killer cell mediated cytotoxicity
positive regulation of DNA biosynthetic process positive regulation of DNA biosynthetic process
Cellular component:
cytosol cytosol
extracellular space extracellular space
mitochondrial intermembrane space mitochondrial intermembrane space
mitochondrion mitochondrion
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, A-2
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: FAD-linked sulfhydryl oxidase ALR
Source organism: Homo sapiens
Length: 205 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMAAPGERGRFHGGNLFFLPGGARSEMMDDLATDARGRGAGRRDAAASASTPAQAPTSDSPVAEDASRRRPCRACVDFKTWMRTQQKRDTKFREDCPPDREELGRHSWAVLHTLAAYYPDLPTPEQQQDMAQFIHLFSKFYPCEECAEDLRKRLCRNHPDTRTRACFTQWLCHLHNEVNRKLGKPDFDCSKVDERWRDGWKDGSCD
UniProtKB AC: P55789 (positions: 91-205)
Coverage: 56%
Name: FAD-linked sulfhydryl oxidase ALR
Source organism: Homo sapiens
Length: 205 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMAAPGERGRFHGGNLFFLPGGARSEMMDDLATDARGRGAGRRDAAASASTPAQAPTSDSPVAEDASRRRPCRACVDFKTWMRTQQKRDTKFREDCPPDREELGRHSWAVLHTLAAYYPDLPTPEQQQDMAQFIHLFSKFYPCEECAEDLRKRLCRNHPDTRTRACFTQWLCHLHNEVNRKLGKPDFDCSKVDERWRDGWKDGSCD
UniProtKB AC: P55789 (positions: 91-205)
Coverage: 56%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: ERV/ALR sulfhydryl oxidase domain
Evidence level: Insufficient evidence (candidate)
Evidence coverage: The full structure participates in mutual synergistic folding.
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 A:
N/A
Chain A-2:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download the CIF file (.cif)
Download this entry's XML file (.xml)
Download this entry's JSON file (.json)
