skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: The Crystal Structure of the Ubiquitin-like Domain of Ribosome Assembly Factor Ytm1 and Characterization of Its Interaction with the AAA-ATPase Midasin

Journal Article · · Journal of Biological Chemistry
 [1];  [1];  [1]
  1. National Inst. of Health, Research Triangle Park, NC (United States)

The synthesis of eukaryotic ribosomes is a complex, energetically demanding process requiring the aid of numerous non-ribosomal factors, such as the PeBoW complex. The mammalian PeBoW complex, composed of Pes1, Bop1, and WDR12, is essential for the processing of the 32S preribosomal RNA. Previous work in Saccharomyces cerevisiae has shown that release of the homologous proteins in this complex (Nop7, Erb1, and Ytm1, respectively) from preribosomal particles requires Rea1 (midasin or MDN1 in humans), a large dynein-like protein. Midasin contains a C-terminal metal ion-dependent adhesion site (MIDAS) domain that interacts with the N-terminal ubiquitin-like (UBL) domain of Ytm1/WDR12 as well as the UBL domain of Rsa4/Nle1 in a later step in the ribosome maturation pathway. Here we present the crystal structure of the UBL domain of the WDR12 homologue from S. cerevisiae at 1.7 Å resolution and demonstrate that human midasin binds to WDR12 as well as Nle1 through their respective UBL domains. Midasin contains a well conserved extension region upstream of the MIDAS domain required for binding WDR12 and Nle1, and the interaction is dependent upon metal ion coordination because removal of the metal or mutation of residues that coordinate the metal ion diminishes the interaction. Mammalian WDR12 displays prominent nucleolar localization that is dependent upon active ribosomal RNA transcription. Here, based upon these results, we propose that release of the PeBoW complex and subsequent release of Nle1 by midasin is a well conserved step in the ribosome maturation pathway in both yeast and mammalian cells.

Research Organization:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health
Grant/Contract Number:
W-31-109-Eng-38
OSTI ID:
1251214
Journal Information:
Journal of Biological Chemistry, Vol. 291, Issue 2; ISSN 0021-9258
Publisher:
American Society for Biochemistry and Molecular BiologyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 24 works
Citation information provided by
Web of Science

References (66)

p53 and ribosome biogenesis stress: The essentials journal April 2014
The Allosteric Role of the AAA + Domain of ChlD Protein from the Magnesium Chelatase of Synechocystis Species PCC 6803 journal August 2013
Ribosome biogenesis dysfunction leads to p53-mediated apoptosis and goblet cell differentiation of mouse intestinal stem/progenitor cells journal June 2015
Overview of the CCP 4 suite and current developments journal March 2011
Yph1p, an ORC-Interacting Protein journal June 2002
Activation of the tumor suppressor p53 upon impairment of ribosome biogenesis journal June 2014
PES1 regulates sensitivity of colorectal cancer cells to anticancer drugs journal February 2013
Notchless Is Required for Axial Skeleton Formation in Mice journal May 2014
Ubiquitin-binding domains journal October 2006
The structure of Erb1-Ytm1 complex reveals the functional importance of a high-affinity binding between two β-propellers during the assembly of large ribosomal subunits in eukaryotes journal October 2015
Driving ribosome assembly journal June 2010
Nucleolar protein PES1 is a marker of neuroblastoma outcome and is associated with neuroblastoma differentiation journal February 2015
Ytm1, Nop7, and Erb1 form a complex necessary for maturation of yeast 66S preribosomes. text January 2005
Contribution of theBOP1 gene, located on 8q24, to colorectal tumorigenesis journal January 2006
The regulation of integrin function by divalent cations journal January 2012
Asociación entre variantes genéticas de enfermedad coronaria y aterosclerosis subclínica: estudio de asociación y metanálisis journal October 2015
Notchless encodes a novel WD40-repeat-containing protein that modulates Notch signaling activity journal December 1998
A time- and cost-efficient system for high-level protein production in mammalian cells journal September 2006
Integrin ligands at a glance journal October 2006
Ribosome Biogenesis in the Yeast Saccharomyces cerevisiae journal November 2013
B23 interacts with PES1 and is involved in nucleolar localization of PES1 journal November 2009
Ubiquitin-like and ubiquitin-associated domain proteins: significance in proteasomal degradation journal May 2009
Interdependence of Pes1, Bop1, and WDR12 Controls Nucleolar Localization and Assembly of the PeBoW Complex Required for Maturation of the 60S Ribosomal Subunit journal March 2007
The nucleolus: structure/function relationship in RNA metabolism: Nucleolus journal September 2010
Nucleolar stress with and without p53 journal August 2014
Mapping the cleavage sites on mammalian pre-rRNAs: Where do we stand? journal July 2012
Interactions among Ytm1, Erb1, and Nop7 Required for Assembly of the Nop7-Subcomplex in Yeast Preribosomes journal July 2008
LAS1L interacts with the mammalian Rix1 complex to regulate ribosome biogenesis journal February 2012
Distribution and Evolution of von Willebrand/Integrin A Domains: Widely Dispersed Domains with Roles in Cell Adhesion and Elsewhere journal October 2002
Mammalian WDR12 is a novel member of the Pes1–Bop1 complex and is required for ribosome biogenesis and cell proliferation journal July 2005
Crystal structure of the 80S yeast ribosome journal December 2012
The AAA-ATPase Rea1 Drives Removal of Biogenesis Factors during Multiple Stages of 60S Ribosome Assembly journal June 2010
The nucleolus as a fundamental regulator of the p53 response and a new target for cancer therapy journal July 2015
Mechanochemical Removal of Ribosome Biogenesis Factors from Nascent 60S Ribosomal Subunits journal September 2009
Eukaryotic ribosome biogenesis at a glance journal October 2013
Wdr12, a Mouse Gene Encoding a Novel WD-Repeat Protein with a Notchless-like Amino-terminal Domain journal January 2002
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
Block of proliferation 1 (BOP1) plays an oncogenic role in hepatocellular carcinoma by promoting epithelial-to-mesenchymal transition journal June 2011
Mysterious Ribosomopathies journal August 2013
WDR12, a Member of Nucleolar PeBoW-Complex, Is Up-Regulated in Failing Hearts and Causes Deterioration of Cardiac Function journal April 2015
PES1 promotes breast cancer by differentially regulating ERα and ERβ journal August 2012
Underexpression of the plant NOTCHLESS gene, encoding a WD-repeat protein, causes pleitropic phenotype during plant development journal November 2006
Overcoming Expression and Purification Problems of RhoGDI Using a Family of “Parallel” Expression Vectors journal February 1999
Ytm1, Nop7, and Erb1 Form a Complex Necessary for Maturation of Yeast 66S Preribosomes journal November 2005
Targeting the nucleolus for cancer intervention journal June 2014
PES1 differentially regulates the expression of ERα and ERβ in ovarian cancer: ERα and ERβ in Ovarian Cancer journal November 2013
New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites journal December 1988
Functional Roles of Ubiquitin-Like Domain (ULD) and Ubiquitin-Binding Domain (UBD) Containing Proteins journal April 2009
Rea1, a Dynein-related Nuclear AAA-ATPase, Is Involved in Late rRNA Processing and Nuclear Export of 60 S Subunits journal November 2004
An atomic resolution view of ICAM recognition in a complex between the binding domains of ICAM-3 and integrin  L 2 journal February 2005
The Structure and Function of the Eukaryotic Ribosome journal May 2012
The Complexity of Human Ribosome Biogenesis Revealed by Systematic Nucleolar Screening of Pre-rRNA Processing Factors journal August 2013
The power of AAA-ATPases on the road of pre-60S ribosome maturation — Molecular machines that strip pre-ribosomal particles journal January 2012
Identification of Human MVB12 Proteins as ESCRT-I Subunits that Function in HIV Budding journal July 2007
A network of assembly factors is involved in remodeling rRNA elements during preribosome maturation journal November 2014
Transcriptional Regulation of PES1 Expression by c-Jun in Colon Cancer journal July 2012
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation journal February 2021
Interactions among Ytm1, Erb1, and Nop7 required for assembly of the Nop7-subcomplex in yeast preribosomes. text January 2008
Ribosome biogenesis in the yeast Saccharomyces cerevisiae. text January 2013
Ytm1, Nop7, and Erb1 form a complex necessary for maturation of yeast 66S preribosomes. text January 2005
Overview of the CCP4 suite and current developments. text January 2011
Ubiquitin-binding domains journal August 2005
A network of assembly factors is involved in remodeling rRNA elements during preribosome maturation journal July 2015
Interactions among Ytm1, Erb1, and Nop7 required for assembly of the Nop7-subcomplex in yeast preribosomes. text January 2008
Ribosome biogenesis in the yeast Saccharomyces cerevisiae. text January 2013
PHENIX: a comprehensive Python-based system for macromolecular structure solution. text January 2010

Cited By (4)

Cryo-EM structure of the essential ribosome assembly AAA-ATPase Rix7 journal January 2019
Ribosome assembly coming into focus journal November 2018
Crystal structures of Rea1-MIDAS bound to its ribosome assembly factor ligands resembling integrin–ligand-type complexes journal July 2019
Structure and interactions of the archaeal motility repression module ArnA–ArnB that modulates archaellum gene expression in Sulfolobus acidocaldarius journal March 2019