Database accession: MF7000999
Name: Dimerization domain of DGCR8 (frog)
PDB ID: 4e5r
Experimental method: X-ray (1.90 Å)
Assembly: Homodimer
Source organism: Xenopus laevis
Primary publication of the structure:
Senturia R, Laganowsky A, Barr I, Scheidemantle BD, Guo F
Dimerization and heme binding are conserved in amphibian and starfish homologues of the microRNA processing protein DGCR8.
(2012) PLoS ONE 7: e39688
PMID: 22768307
Abstract:
Human DiGeorge Critical Region 8 (DGCR8) is an essential microRNA (miRNA) processing factor that is activated via direct interaction with Fe(III) heme. In order for DGCR8 to bind heme, it must dimerize using a dimerization domain embedded within its heme-binding domain (HBD). We previously reported a crystal structure of the dimerization domain from human DGCR8, which demonstrated how dimerization results in the formation of a surface important for association with heme. Here, in an attempt to crystallize the HBD, we search for DGCR8 homologues and show that DGCR8 from Patiria miniata (bat star) also binds heme. The extinction coefficients (ε) of DGCR8-heme complexes are determined; these values are useful for biochemical analyses and allow us to estimate the heme occupancy of DGCR8 proteins. Additionally, we present the crystal structure of the Xenopus laevis dimerization domain. The structure is very similar to that of human DGCR8. Our results indicate that dimerization and heme binding are evolutionarily conserved properties of DGCR8 homologues not only in vertebrates, but also in at least some invertebrates.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
double-stranded RNA binding double-stranded RNA binding
heme binding heme binding
identical protein binding identical protein binding
primary miRNA binding primary miRNA binding
Biological process:
primary miRNA processing primary miRNA processing
Cellular component:
microprocessor complex microprocessor complex
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: MGC78846 protein
Source organism: Xenopus laevis
Length: 772 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMEECEEVAPFPEVNGHDVTEMNPASPPPLPPEEEPPPPPLQTSSDAEVMDVGSGGDGQSQTPAGDLQQNNGLQLFTKGSTSYKSHRTVLDPFHSDQSPRTARHAPSNKRFTPDLKLLKDVKVSVSFTESCRSKDRHVLYTGLECEGSLHGGSNMNSVNGDMYVCPFAGSSNGNVTDSIEITLKKNYEPEIEQEKKVEYAVLDELEDFTENVMDVDEDGAEFVSESILQREKIDEEALIYSYEDEFDNDVDALLEESLHTPKKRRIDEKYDIDSDHQSDGESSVQPMVTKIKTVLKSRGRPPTEPLPDGWIMTFHNSGLPVYLHRETRVVTWSRPYFLGTGSIRKHDPPISSIPCLHYKKMKDNDIKEQSNDVTSALVSVSSSTKSSDTSHNSEEPDTTAADSFVSDERESVSEVAQGALGQVKAKVEVCKDESINLEDFRSYLEKRFDFEQVTVKKFRTWAERRQFNREMKRKQAECERPILPANQKLITLSVQDAPTKKEFVINPNGKSEVCILHEYMQRVLKVRPVYNFFECENPSEPFGASVIINGVTYGTGTASSKKLAKNKAARATLEILIPDFVKQTCIEKPKDTDELEYFNHISIEDSRVYELTNKAGLLSPYQILHECLKRNHGMGDTSIKFEVIPGKNQKSEYVMTCGKHTVRGWCKNKRVGKQLASQKILQLLHPHVKNWGSLLRMYGRENSKIVKQETADKSVIELQQFAKKNKPNLHILNKLQEEMRRLAQEREETRKKPKMTIVESAQPGSEPLCTVDV
UniProtKB AC: Q6IRB5 (positions: 300-355)
Coverage: 7%
Name: MGC78846 protein
Source organism: Xenopus laevis
Length: 772 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMEECEEVAPFPEVNGHDVTEMNPASPPPLPPEEEPPPPPLQTSSDAEVMDVGSGGDGQSQTPAGDLQQNNGLQLFTKGSTSYKSHRTVLDPFHSDQSPRTARHAPSNKRFTPDLKLLKDVKVSVSFTESCRSKDRHVLYTGLECEGSLHGGSNMNSVNGDMYVCPFAGSSNGNVTDSIEITLKKNYEPEIEQEKKVEYAVLDELEDFTENVMDVDEDGAEFVSESILQREKIDEEALIYSYEDEFDNDVDALLEESLHTPKKRRIDEKYDIDSDHQSDGESSVQPMVTKIKTVLKSRGRPPTEPLPDGWIMTFHNSGLPVYLHRETRVVTWSRPYFLGTGSIRKHDPPISSIPCLHYKKMKDNDIKEQSNDVTSALVSVSSSTKSSDTSHNSEEPDTTAADSFVSDERESVSEVAQGALGQVKAKVEVCKDESINLEDFRSYLEKRFDFEQVTVKKFRTWAERRQFNREMKRKQAECERPILPANQKLITLSVQDAPTKKEFVINPNGKSEVCILHEYMQRVLKVRPVYNFFECENPSEPFGASVIINGVTYGTGTASSKKLAKNKAARATLEILIPDFVKQTCIEKPKDTDELEYFNHISIEDSRVYELTNKAGLLSPYQILHECLKRNHGMGDTSIKFEVIPGKNQKSEYVMTCGKHTVRGWCKNKRVGKQLASQKILQLLHPHVKNWGSLLRMYGRENSKIVKQETADKSVIELQQFAKKNKPNLHILNKLQEEMRRLAQEREETRKKPKMTIVESAQPGSEPLCTVDV
UniProtKB AC: Q6IRB5 (positions: 300-355)
Coverage: 7%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: -
Evidence level: Indirect evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
SEC analyses indicated that the bat star HBD is a dimer in solution. The subunits are held together by an extensive interface mainly mediated by hydrophobic interactions. The WW motif folds into three β-strands (β1–β3) and a fourth β-strand (β4) interacts with the WW motif of the partner subunit, forming a continuous β-sheet and resulting in an apparently domain-swapped dimer (PMID:22768307).
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). No related structure was found in the MFIB database.
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