1t6o
From Proteopedia
Nucleocapsid-binding domain of the measles virus P protein (amino acids 457-507) in complex with amino acids 486-505 of the measles virus N protein
Structural highlights
FunctionPHOSP_MEASM Essential cofactor of the RNA polymerase L that plays a central role in the transcription and replication by forming the polymerase complex with RNA polymerase L and recruiting L to the genomic N-RNA template for RNA synthesis (PubMed:23022562). Plays also a central role in the encapsidation of nascent RNA chains by forming the encapsidation complex with the nucleocapsid protein N (N-P complex) (By similarity). Acts as a chaperone for newly synthesized free N protein, so-called N0, allowing encapsidation of nascent RNA chains during replication (By similarity). The nucleoprotein protein N prevents excessive phosphorylation of P, which leads to down-regulation of viral transcription/ replication (PubMed:23022562). Participates, together with N, in the formation of viral factories (viroplasms), which are large inclusions in the host cytoplasm where replication takes place (PubMed:31375591).[UniProtKB:P06162][1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe nucleocapsid of measles virus is the template for viral RNA synthesis and is generated through packaging of the genomic RNA by the nucleocapsid protein (N). The viral polymerase associates with the nucleocapsid through a small, trihelical binding domain at the carboxyl terminus of the phosphoprotein (P). Translocation of the polymerase along the nucleocapsid during RNA synthesis is thought to involve the repeated attachment and release of the binding domain. We have investigated the interaction between the binding domain from measles P (amino acids 457-507) and the sequence it recognizes within measles N (amino acids 477-505). By using both solution NMR spectroscopy and x-ray crystallography, we show that N(487-503) binds as a helix to the surface created by the second (alpha2) and third (alpha3) helices of P(457-507), in an orientation parallel to the helix alpha3, creating a four-helix bundle. The binding interface is tightly packed and dominated by hydrophobic amino acids. Binding and folding of N(487-503) are coupled. However, when not bound to P, N(487-503) does not resemble a statistical random coil but instead exists in a loosely structured state that mimics the bound conformation. We propose that before diffusional encounter, the ensemble of accessible conformations for N(487-503) is biased toward structures capable of binding P, facilitating rapid association of the two proteins. This study provides a structural analysis of polymerase-template interactions in a paramyxovirus and presents an example of a protein-protein interaction that must be only transiently maintained as part of its normal function. Structural basis for the attachment of a paramyxoviral polymerase to its template.,Kingston RL, Hamel DJ, Gay LS, Dahlquist FW, Matthews BW Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8301-6. Epub 2004 May 24. PMID:15159535[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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