Structural Analysis Reveals Features of Ribosome Assembly Factor Nsa1/WDR74 Important for Localization and Interaction with Rix7/NVL2

Structure. 2017 May 2;25(5):762-772.e4. doi: 10.1016/j.str.2017.03.008.

Yu-Hua Lo ¹, Erin M Romes ¹, Monica C Pillon ¹, Mack Sobhany ¹, Robin E Stanley ²

Affiliations

1 Signal Transduction Laboratory, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T. W. Alexander Drive, Research Triangle Park, NC 27709, USA.
2 Signal Transduction Laboratory, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T. W. Alexander Drive, Research Triangle Park, NC 27709, USA. Electronic address: robin.stanley@nih.gov.

PMID: 28416111 DOI: 10.1016/j.str.2017.03.008

Abstract

Ribosome assembly is a complex process that requires hundreds of essential assembly factors, including Rix7 (NVL2 in mammals) and Nsa1 (WDR74 in mammals). Rix7 is a type II double ring, AAA-ATPase, which is closely related to the well-known Cdc48/p97. Previous studies in Saccharomyces cerevisiae suggest that Rix7 mediates the release of Nsa1 from nucleolar pre-60S particles; however, the underlying mechanisms of this release are unknown. Through multiple structural analyses we show that S. cerevisiae Nsa1 is composed of an N-terminal seven-bladed WD40 domain followed by a lysine-rich C terminus that extends away from the WD40 domain and is required for nucleolar localization. Co-immunoprecipitation assays with the mammalian homologs identified a well-conserved interface within WDR74 that is important for its association with NVL2. We further show that WDR74 associates with the D1 AAA domain of NVL2, which represents a novel mode of binding of a substrate with a type II AAA-ATPase.

Keywords

AAA-ATPase; WD40 domain; pre-rRNA processing; ribosome assembly.

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