Structural basis for recognition and sequestration of UUUOH 3′ temini of nascent RNA polymerase III transcripts by La, a rheumatic disease autoantigen Journal Article
| Authors: | Teplova, M.; Yuan, Y. R.; Phan, A. T.; Malinina, L.; Ilin, S.; Teplov, A.; Patel, D. J. |
| Article Title: | Structural basis for recognition and sequestration of UUUOH 3′ temini of nascent RNA polymerase III transcripts by La, a rheumatic disease autoantigen |
| Abstract: | The nuclear phosphoprotein La was identified as an autoantigen in patients with systemic lupus erythematosus and Sjogren's syndrome. La binds to and protects the UUUOH 3′ terminii of nascent RNA polymerase III transcripts from exonuclease digestion. We report the 1.85 Å crystal structure of the N-terminal domain of human La, consisting of La and RRM1 motifs, bound to r(U1-G2-C3-U4-G5-U6-U7-U8-U9OH). The U7-U8-U9 OH 3′ end, in a splayed-apart orientation, is sequestered within a basic and aromatic amino acid-lined cleft between the La and RRM1 motifs. The specificity-determining U8 residue bridges both motifs, in part through unprecedented targeting of the β sheet edge, rather than the anticipated face, of the RRM1 motif. Our structural observations, supported by mutation studies of both La and RNA components, illustrate the principles behind RNA sequestration by a rheumatic disease autoantigen, whereby the UUU OH 3′ ends of nascent RNA transcripts are protected during downstream processing and maturation events. ©2006 Elsevier Inc. |
| Keywords: | gene mutation; mutation; protein conformation; protein domain; protein motif; protein protein interaction; protein targeting; protein binding; genetic transcription; transcription, genetic; rna; protein processing; amino terminal sequence; molecular recognition; autoantigen; autoantigens; ribonucleoproteins; crystal structure; hydrogen bonding; models, molecular; crystallography, x-ray; protein structure; enzyme substrate complex; downstream processing; macromolecular substances; uracil; rheumatic disease; beta sheet; dna directed rna polymerase iii; rna polymerase iii; aromatic amino acid; la antigen |
| Journal Title: | Molecular Cell |
| Volume: | 21 |
| Issue: | 1 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2006-01-06 |
| Start Page: | 75 |
| End Page: | 85 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2005.10.027 |
| PUBMED: | 16387655 |
| PROVIDER: | scopus |
| PMCID: | PMC4689297 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 46" - "Export Date: 4 June 2012" - "CODEN: MOCEF" - "Source: Scopus" |
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