1d4r
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29-mer fragment of human srp rna helix 6
OverviewOverview
BACKGROUND: The mammalian signal recognition particle (SRP) is an, essential cytoplasmic ribonucleoprotein complex involved in targeting, signal-peptide-containing proteins to the endoplasmic reticulum. Assembly, of the SRP requires protein SRP19 to bind first to helix 6 of the SRP RNA, before the signal-peptide-recognizing protein, SRP54, can bind to helix 8, of the RNA. Helix 6 is closed by a GGAG tetraloop, which has been shown to, form part of the SRP19-binding site. RESULTS: The high-resolution (2.0 A), structure of a fragment of human SRP RNA comprising 29 nucleotides of, helix 6 has been determined using the multiple anomalous dispersion (MAD), method and bromine-labelled RNA. In the crystal the molecule forms 28-mer, duplexes rather than the native monomeric hairpin structure, although two, chemically equivalent 11 base pair stretches of the duplex represent the, presumed native structure. The duplex has highly distorted A-RNA geometry, caused by the occurrence of several non-Watson-Crick base pairs. These, include a 5'-GGAG-3'/3'-GAGG-5' purine bulge (which replaces the, tetraloop) and a 5'-AC-3'/3'-CA-5' tandem mismatch that, depending on the, protonation state of the adenine bases, adopts a different conformation in, the two native-like parts of the structure. The structure also shows the, 2'3'-cyclic phosphate reaction product of the hammerhead ribozyme cleavage, reaction. CONCLUSIONS: The 29-mer RNA is the first RNA structure of the, human SRP and provides some insight into the binding mode of SRP19. The, observed strong irregularities of the RNA helix make the major groove wide, enough and flat enough to possibly accommodate an alpha helix of SRP19., The variety of non-canonical base pairs observed enlarges the limited, repertoire of irregular RNA folds known to date and the observed, conformation of the 2'3'-cyclic phosphate containing Ade29 is consistent, with the current understanding of the hammerhead ribozyme reaction, mechanism.
About this StructureAbout this Structure
1D4R is a Protein complex structure of sequences from [1] with MG as ligand. Full crystallographic information is available from OCA.
ReferenceReference
The 2 A structure of helix 6 of the human signal recognition particle RNA., Wild K, Weichenrieder O, Leonard GA, Cusack S, Structure. 1999 Nov 15;7(11):1345-52. PMID:10574798
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