Orientation of the central domains of KSRP and its implications for the interaction with the RNA targets.
KSRP is a multi-domain RNA-binding protein that recruits the exosome-containing mRNA degradation complex to mRNAs coding for cellular proliferation and inflammatory response factors. The selectivity of this mRNA degradation mechanism relies on KSRP recognition of AU-rich elements in the mRNA 3'UTR, that is mediated by KSRP's KH domains. Our structural analysis shows that the inter-domain linker orients the two central KH domains of KSRP-and their RNA-binding surfaces-creating a two-domain unit. We also show that this inter-domain arrangement is important to the interaction with KSRP's RNA targets.
Díaz-Moreno
Irene
I
Molecular Structure Division, MRC National Institute for Medical Research, The Ridgeway, London, UK.
Hollingworth
David
D
Kelly
Geoff
G
Martin
Stephen
S
García-Mayoral
MaríaFlor
M
Briata
Paola
P
Gherzi
Roberto
R
Ramos
Andres
A
D020413:3' Untranslated Regions; D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism
D020413:3' Untranslated Regions; C105789:KHSRP protein, human; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D012313:RNA
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