2rre
Structure and function of the N-terminal nucleolin binding domain of nuclear valocine containing protein like 2 (NVL2) harboring a nucleolar localization signal
Structural highlights
FunctionNVL_MOUSE Participates in the assembly of the telomerase holoenzyme and effecting of telomerase activity via its interaction with TERT. Involved in both early and late stages of the pre-rRNA processing pathways. Spatiotemporally regulates 60S ribosomal subunit biogenesis in the nucleolus. Catalyzes the release of specific assembly factors, such as WDR74, from pre-60S ribosomal particles through the ATPase activity.[UniProtKB:O15381] Publication Abstract from PubMedThe N-terminal regions of AAA-ATPases (ATPase associated with various cellular activities) often contain a domain that defines the distinct functions of the enzymes, such as substrate specificity and subcellular localization. As described herein, we have determined the solution structure of an N-terminal unique domain isolated from nuclear valosin-containing protein (VCP)-like protein 2 (NVL2(UD)). NVL2(UD) contains three alpha helices with an organization resembling that of a winged helix motif, whereas a pair of beta-strands is missing. The structure is unique and distinct from those of other known type II AAA-ATPases, such as VCP. Consequently, we identified nucleolin from a HeLa cell extract as a binding partner of this domain. Nucleolin contains a long ( approximately 300 amino acids) intrinsically unstructured region, followed by the four tandem RNA recognition motifs and the C-terminal glycine/arginine-rich domain. Binding analyses revealed that NVL2(UD) potentially binds to any of the combinations of two successive RNA binding domains in the presence of RNA. Furthermore, NVL2(UD) has a characteristic loop, in which the key basic residues RRKR are exposed to the solvent at the edge of the molecule. The mutation study showed that these residues are necessary and sufficient for nucleolin-RNA complex binding as well as nucleolar localization. Based on the observations presented above, we propose that NVL2 serves as an unfoldase for the nucleolin-RNA complex. As inferred from its RNA dependence and its ATPase activity, NVL2 might facilitate the dissociation and recycling of nucleolin, thereby promoting efficient ribosome biogenesis. Structure and function of the N-terminal nucleolin binding domain of nuclear valosin-containing protein-like 2 (NVL2) harboring a nucleolar localization signal.,Fujiwara Y, Fujiwara K, Goda N, Iwaya N, Tenno T, Shirakawa M, Hiroaki H J Biol Chem. 2011 Jun 17;286(24):21732-41. Epub 2011 Apr 7. PMID:21474449[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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