Database accession: MF7000824
Name: Human Dcps
PDB ID: 1xml
Experimental method: X-ray (2.00 Å)
Assembly: Homodimer
Source organism: Homo sapiens
Primary publication of the structure:
Chen N, Walsh MA, Liu Y, Parker R, Song H
Crystal structures of human DcpS in ligand-free and m7GDP-bound forms suggest a dynamic mechanism for scavenger mRNA decapping.
(2005) J. Mol. Biol. 347: 707-18
PMID: 15769464
Abstract:
Eukaryotic cells utilize DcpS, a scavenger decapping enzyme, to degrade the residual cap structure following 3'-5' mRNA decay, thereby preventing the premature decapping of the capped long mRNA and misincorporation of methylated nucleotides in nucleic acids. We report the structures of DcpS in ligand-free form and in a complex with m7GDP. apo-DcpS is a symmetric dimer, strikingly different from the asymmetric dimer observed in the structures of DcpS with bound cap analogues. In contrast, and similar to the m7GpppG-DcpS complex, DcpS with bound m7GDP is an asymmetric dimer in which the closed state appears to be the substrate-bound complex, whereas the open state mimics the product-bound complex. Comparisons of these structures revealed conformational changes of both the N-terminal swapped-dimeric domain and the cap-binding pocket upon cap binding. Moreover, Tyr273 in the cap-binding pocket displays remarkable conformational changes upon cap binding. Mutagenesis and biochemical analysis suggest that Tyr273 seems to play an important role in cap binding and product release. Examination of the crystallographic B-factors indicates that the N-terminal domain in apo-DcpS is inherently flexible, and in a dynamic state ready for substrate binding and product release.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
5'-(N(7)-methyl 5'-triphosphoguanosine)-[mRNA] diphosphatase activity 5'-(N(7)-methyl 5'-triphosphoguanosine)-[mRNA] diphosphatase activity
identical protein binding identical protein binding
RNA 7-methylguanosine cap binding RNA 7-methylguanosine cap binding
RNA exonuclease activity RNA exonuclease activity
Biological process:
deadenylation-dependent decapping of nuclear-transcribed mRNA deadenylation-dependent decapping of nuclear-transcribed mRNA
mRNA cis splicing, via spliceosome mRNA cis splicing, via spliceosome
mRNA methylguanosine-cap decapping mRNA methylguanosine-cap decapping
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
Cellular component:
cytoplasm cytoplasm
cytosol cytosol
mitochondrion mitochondrion
nucleoplasm nucleoplasm
nucleus nucleus
P-body P-body
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, B
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: m7GpppX diphosphatase
Source organism: Homo sapiens
Length: 337 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMADAAPQLGKRKRELDVEEAHAASTEEKEAGVGNGTCAPVRLPFSGFRLQKVLRESARDKIIFLHGKVNEASGDGDGEDAVVILEKTPFQVEQVAQLLTGSPELQLQFSNDIYSTYHLFPPRQLNDVKTTVVYPATEKHLQKYLRQDLRLIRETGDDYRNITLPHLESQSLSIQWVYNILDKKAEADRIVFENPDPSDGFVLIPDLKWNQQQLDDLYLIAICHRRGIRSLRDLTPEHLPLLRNILHQGQEAILQRYRMKGDHLRVYLHYLPSYYHLHVHFTALGFEAPGSGVERAHLLAEVIENLECDPRHYQQRTLTFALRADDPLLKLLQEAQQS
UniProtKB AC: Q96C86 (positions: 38-336)
Coverage: 88%
Name: m7GpppX diphosphatase
Source organism: Homo sapiens
Length: 337 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMADAAPQLGKRKRELDVEEAHAASTEEKEAGVGNGTCAPVRLPFSGFRLQKVLRESARDKIIFLHGKVNEASGDGDGEDAVVILEKTPFQVEQVAQLLTGSPELQLQFSNDIYSTYHLFPPRQLNDVKTTVVYPATEKHLQKYLRQDLRLIRETGDDYRNITLPHLESQSLSIQWVYNILDKKAEADRIVFENPDPSDGFVLIPDLKWNQQQLDDLYLIAICHRRGIRSLRDLTPEHLPLLRNILHQGQEAILQRYRMKGDHLRVYLHYLPSYYHLHVHFTALGFEAPGSGVERAHLLAEVIENLECDPRHYQQRTLTFALRADDPLLKLLQEAQQS
UniProtKB AC: Q96C86 (positions: 40-336)
Coverage: 88%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Scavenger mRNA decapping enzyme (DcpS)
Evidence level: Indirect evidence
Evidence coverage: Only some parts of the structure participates in mutual synergistic folding.
Complex Evidence:
Multidomain structure, where the domain-swapped N-terminal domain is responsible for dimerization. The extensive interface, symmetry, topology, beta sheet augmentation and buried surface area suggest that the N-terminal dimerization domain behaves as a single rigid domain and the monomers would not be stable on their own. Gel-filtration chromatography also suggested a dimeric form (PMID:15068804).
Chain B:
N/A
Chain A:
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)
