1h95
Solution structure of the single-stranded DNA-binding Cold Shock Domain (CSD) of human Y-box protein 1 (YB1) determined by NMR (10 lowest energy structures)
Structural highlights
FunctionYBOX1_HUMAN Mediates pre-mRNA alternative splicing regulation. Binds to splice sites in pre-mRNA and regulates splice site selection. Binds and stabilizes cytoplasmic mRNA. Contributes to the regulation of translation by modulating the interaction between the mRNA and eukaryotic initiation factors (By similarity). Regulates the transcription of numerous genes. Its transcriptional activity on the multidrug resistance gene MDR1 is enhanced in presence of the APEX1 acetylated form at 'Lys-6' and 'Lys-7'. Binds to promoters that contain a Y-box (5'-CTGATTGGCCAA-3'), such as MDR1 and HLA class II genes. Promotes separation of DNA strands that contain mismatches or are modified by cisplatin. Has endonucleolytic activity and can introduce nicks or breaks into double-stranded DNA (in vitro). May play a role in DNA repair. Component of the CRD-mediated complex that promotes MYC mRNA stability. Binds preferentially to the 5'-[CU]CUGCG-3' motif in vitro.[1] [2] [3] [4] [5] [6] [7] [8] The secreted form acts as an extracellular mitogen and stimulates cell migration and proliferation. 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 human Y-box protein 1 (YB-1) is a member of the Y-box protein family, a class of proteins involved in transcriptional and translational regulation of a wide range of genes. Here, we report the solution structure of the cold-shock domain (CSD) of YB-1, which is thought to be responsible for nucleic acid binding. It is the first structure solved of a eukaryotic member of the cold-shock protein family and consists of a closed five-stranded anti-parallel beta-barrel capped by a long flexible loop. The structure of CSD is similar to the OB-fold and a comparison with bacterial cold-shock proteins shows that its structural properties are conserved from bacteria to man. Our data suggest the presence of a DNA-binding site consisting of a patch of positively charged and aromatic residues on the surface of the beta-barrel. Further, it is shown that CSD, which has a preference for binding single-stranded pyrimidine-rich sequences, binds weakly and hardly specifically to DNA. Binding affinities reported for intact YB-1 indicate that domains other than the CSD play a role in DNA binding of YB-1. The solution structure and DNA-binding properties of the cold-shock domain of the human Y-box protein YB-1.,Kloks CP, Spronk CA, Lasonder E, Hoffmann A, Vuister GW, Grzesiek S, Hilbers CW J Mol Biol. 2002 Feb 15;316(2):317-26. PMID:11851341[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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