6w38
Crystal structure of the FAM46C/Plk4 complex
Structural highlights
FunctionTET5C_HUMAN Nucleotidyltransferase that act as a non-canonical poly(A) RNA polymerase which enhances mRNA stability and gene expression. Mainly targets mRNAs encoding endoplasmic reticulum-targeted protein and may be involved in induction of cell death.[1] [2] (Microbial infection) Seems to enhance replication of some viruses, including yellow fever virus, in response to type I interferon.[3] Publication Abstract from PubMedFAM46C, a non-canonical poly(A) polymerase, is frequently mutated in multiple myeloma. Loss of function of FAM46C promotes cell survival of multiple myeloma, suggesting a tumor-suppressive role. FAM46C is also essential for fastening sperm head and flagellum, indispensable for male fertility. The molecular mechanisms of these functions of FAM46C remain elusive. We report the crystal structure of FAM46C to provide the basis for its poly(A) polymerase activity and rationalize mutations associated with multiple myeloma. In addition, we found that FAM46C interacts directly with the serine/threonine kinase Plk4, the master regulator of centrosome duplication. We present the structure of FAM46C in complex with the Cryptic Polo-Box 1-2 domains of Plk4. Our structure-based mutational analyses show that the interaction with Plk4 recruits FAM46C to centrosomes. Our data suggest that Plk4-mediated localization of FAM46C enables its regulation of centrosome structure and functions, which may underlie the roles for FAM46C in cell proliferation and sperm development. Structural and Functional Analyses of the FAM46C/Plk4 Complex.,Chen H, Lu D, Shang G, Gao G, Zhang X Structure. 2020 May 12. pii: S0969-2126(20)30169-6. doi:, 10.1016/j.str.2020.04.023. PMID:32433990[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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