Database accession: MF7000868
Name: Human ALR, mutant C142S
PDB ID: 3u2l
Experimental method: X-ray (1.95 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, Tokatlidis K
An electron-transfer path through an extended disulfide relay system: the case of the redox protein ALR.
(2012) J. Am. Chem. Soc. 134: 1442-5
PMID: 22224850
Abstract:
The oxidative folding mechanism in the intermembrane space of human mitochondria underpins a disulfide relay system consisting of the import receptor Mia40 and the homodimeric FAD-dependent thiol oxidase ALR. The flavoprotein ALR receives two electrons per subunit from Mia40, which are then donated through one-electron reactions to two cytochrome c molecules, thus mediating a switch from two-electron to one-electron transfer. We dissect here the mechanism of the electron flux within ALR, characterizing at the atomic level the ALR intermediates that allow electrons to rapidly flow to cytochrome c. The intermediate critical for the electron-transfer process implies the formation of a specific inter-subunit disulfide which exclusively allows electron flow from Mia40 to FAD. This finding allows us to present a complete model for the electron-transfer pathway in ALR.
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)
