Structural highlights
Function
[LA_HUMAN] Binds to the 3' poly(U) terminii of nascent RNA polymerase III transcripts, protecting them from exonuclease digestion and facilitating their folding and maturation.[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 PubMed
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 UUU(OH) 3' terminii of nascent RNA polymerase III transcripts from exonuclease digestion. We report the 1.85 angstroms 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-U9OH 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 beta 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.
Structural basis for recognition and sequestration of UUU(OH) 3' temini of nascent RNA polymerase III transcripts by La, a rheumatic disease autoantigen.,Teplova M, Yuan YR, Phan AT, Malinina L, Ilin S, Teplov A, Patel DJ Mol Cell. 2006 Jan 6;21(1):75-85. PMID:16387655[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chambers JC, Kenan D, Martin BJ, Keene JD. Genomic structure and amino acid sequence domains of the human La autoantigen. J Biol Chem. 1988 Dec 5;263(34):18043-51. PMID:3192525
- ↑ Gottlieb E, Steitz JA. Function of the mammalian La protein: evidence for its action in transcription termination by RNA polymerase III. EMBO J. 1989 Mar;8(3):851-61. PMID:2470590
- ↑ Teplova M, Yuan YR, Phan AT, Malinina L, Ilin S, Teplov A, Patel DJ. Structural basis for recognition and sequestration of UUU(OH) 3' temini of nascent RNA polymerase III transcripts by La, a rheumatic disease autoantigen. Mol Cell. 2006 Jan 6;21(1):75-85. PMID:16387655 doi:10.1016/j.molcel.2005.10.027
