6lms
From Proteopedia
Solution NMR structure cold shock domain of YB1 from Homo sapiens
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. Publication Abstract from PubMedHuman Y-box binding protein 1 (YB-1) is a multifunctional protein and overexpressed in many types of cancer. It specifically recognizes DNA/RNA through a cold shock domain (CSD) and regulates nucleic acid metabolism. The C-terminal extension of CSD and the phosphorylation of S102 are indispensable for YB-1 function. Until now, the roles of the C-terminal extension and phosphorylation in gene transcription and translation are still largely unknown. Here, we solved the structure of human YB-1 CSD with a C-terminal extension sequence (CSDex). The structure reveals that the extension interacts with several residues in the conventional CSD and adopts a rigid structure instead of being disordered. Either deletion of this extension or phosphorylation of S102 destabilizes the protein and results in partial unfolding. Structural characterization of CSDex in complex with a ssDNA heptamer shows that all the seven nucleotides are involved in DNA-protein interactions and the C-terminal extension provides a unique DNA binding site. Our DNA-binding study indicates that CSDex can recognize more DNA sequences than previously thought and the phosphorylation reduces its binding to ssDNA dramatically. Our results suggest that gene transcription and translation can be regulated by changing the affinity of CSDex binding to DNA and RNA through phosphorylation, respectively. Structural basis of DNA binding to human YB-1 cold shock domain regulated by phosphorylation.,Zhang J, Fan JS, Li S, Yang Y, Sun P, Zhu Q, Wang J, Jiang B, Yang D, Liu M Nucleic Acids Res. 2020 Sep 18;48(16):9361-9371. doi: 10.1093/nar/gkaa619. PMID:32710623[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Li S | Yang Y | Zhang J
