DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Structure and Interactions of the CS Domain of Human H/ACA RNP Assembly Protein Shq1

Abstract

Shq1 is an essential protein involved in the early steps of biogenesis and assembly of H/ACA ribonucleoprotein particles (RNPs). Shq1 binds to dyskerin (Cbf5 in yeast) at an early step of H/ACA RNP assembly and is subsequently displaced by the H/ACA RNA. Shq1 contains an N-terminal CS and a C-terminal Shq1-specific domain (SSD). Dyskerin harbors many mutations associated with dyskeratosis congenita. Structures of yeast Shq1 SSD bound to Cbf5 revealed that only a subset of these mutations is in the SSD binding site, implicating another subset in the putative CS binding site. Here in this paper, we present the crystal structure of human Shq1 CS (hCS) and the nuclear magnetic resonance (NMR) and crystal structures of hCS containing a serine substitution for proline 22 that is associated with some prostate cancers. The structure of hCS is similar to yeast Shq1 CS domain (yCS) and consists of two β-sheets that form an immunoglobulin-like β-sandwich fold. The N-terminal affinity tag sequence AHHHHHH associates with a neighboring protein in the crystal lattice to form an extra β-strand. Deletion of this tag was required to get spectra suitable for NMR structure determination, while the tag was required for crystallization. NMR chemical shift perturbation (CSP)more » experiments with peptides derived from putative CS binding sites on dyskerin and Cbf5 revealed a conserved surface on CS important for Cbf5/dyskerin binding. A HADDOCK (high-ambiguity-driven protein-protein docking) model of a Shq1-Cbf5 complex that defines the position of CS domain in the pre-H/ACA RNP was calculated using the CSP data.« less

Authors:
 [1];  [2];  [3];  [4]
  1. Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry; Indian Inst. of Science, Bangalore (India)
  2. Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry; Univ. of Texas, San Antonio, TX (United States). Dept. of Biochemistry
  3. Univ. of California, Los Angeles, CA (United States). Inst. for Genomics and Proteomics
  4. Univ. of California, Los Angeles, CA (United States). Dept. of Chemistry and Biochemistry; Univ. of California, Los Angeles, CA (United States). Inst. for Genomics and Proteomics
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH); USDOE; National Science Foundation (NSF)
OSTI Identifier:
1170018
Alternate Identifier(s):
OSTI ID: 1242546
Grant/Contract Number:  
FC0302ER63421; AC02-06CH11357; P41 RR015301; P41 GM103403; MCB1022379; GM048123
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Molecular Biology
Additional Journal Information:
Journal Volume: 427; Journal Issue: 4; Journal ID: ISSN 0022-2836
Publisher:
Elsevier
Country of Publication:
United States
Language:
ENGLISH
Subject:
60 APPLIED LIFE SCIENCES; NMR; chemical shift perturbation; X-ray crystal structure; dyskerin and Cbf5; telomerase

Citation Formats

Singh, Mahavir, Wang, Zhonghua, Cascio, Duilio, and Feigon, Juli. Structure and Interactions of the CS Domain of Human H/ACA RNP Assembly Protein Shq1. United States: N. p., 2014. Web. doi:10.1016/j.jmb.2014.12.012.
Singh, Mahavir, Wang, Zhonghua, Cascio, Duilio, & Feigon, Juli. Structure and Interactions of the CS Domain of Human H/ACA RNP Assembly Protein Shq1. United States. https://doi.org/10.1016/j.jmb.2014.12.012
Singh, Mahavir, Wang, Zhonghua, Cascio, Duilio, and Feigon, Juli. Mon . "Structure and Interactions of the CS Domain of Human H/ACA RNP Assembly Protein Shq1". United States. https://doi.org/10.1016/j.jmb.2014.12.012. https://www.osti.gov/servlets/purl/1170018.
@article{osti_1170018,
title = {Structure and Interactions of the CS Domain of Human H/ACA RNP Assembly Protein Shq1},
author = {Singh, Mahavir and Wang, Zhonghua and Cascio, Duilio and Feigon, Juli},
abstractNote = {Shq1 is an essential protein involved in the early steps of biogenesis and assembly of H/ACA ribonucleoprotein particles (RNPs). Shq1 binds to dyskerin (Cbf5 in yeast) at an early step of H/ACA RNP assembly and is subsequently displaced by the H/ACA RNA. Shq1 contains an N-terminal CS and a C-terminal Shq1-specific domain (SSD). Dyskerin harbors many mutations associated with dyskeratosis congenita. Structures of yeast Shq1 SSD bound to Cbf5 revealed that only a subset of these mutations is in the SSD binding site, implicating another subset in the putative CS binding site. Here in this paper, we present the crystal structure of human Shq1 CS (hCS) and the nuclear magnetic resonance (NMR) and crystal structures of hCS containing a serine substitution for proline 22 that is associated with some prostate cancers. The structure of hCS is similar to yeast Shq1 CS domain (yCS) and consists of two β-sheets that form an immunoglobulin-like β-sandwich fold. The N-terminal affinity tag sequence AHHHHHH associates with a neighboring protein in the crystal lattice to form an extra β-strand. Deletion of this tag was required to get spectra suitable for NMR structure determination, while the tag was required for crystallization. NMR chemical shift perturbation (CSP) experiments with peptides derived from putative CS binding sites on dyskerin and Cbf5 revealed a conserved surface on CS important for Cbf5/dyskerin binding. A HADDOCK (high-ambiguity-driven protein-protein docking) model of a Shq1-Cbf5 complex that defines the position of CS domain in the pre-H/ACA RNP was calculated using the CSP data.},
doi = {10.1016/j.jmb.2014.12.012},
journal = {Journal of Molecular Biology},
number = 4,
volume = 427,
place = {United States},
year = {Mon Dec 29 00:00:00 EST 2014},
month = {Mon Dec 29 00:00:00 EST 2014}
}

Journal Article:

Citation Metrics:
Cited by: 7 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Box H/ACA Small Ribonucleoproteins
journal, March 2010


Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs
journal, March 2007

  • Matera, A. Gregory; Terns, Rebecca M.; Terns, Michael P.
  • Nature Reviews Molecular Cell Biology, Vol. 8, Issue 3
  • DOI: 10.1038/nrm2124

The many facets of H/ACA ribonucleoproteins
journal, March 2005


H/ACA guide RNAs, proteins and complexes
journal, June 2007


RNA pseudouridylation: new insights into an old modification
journal, April 2013


A Box H/ACA Small Nucleolar RNA-Like Domain at the Human Telomerase RNA 3′ End
journal, January 1999

  • Mitchell, James R.; Cheng, Jeffrey; Collins, Kathleen
  • Molecular and Cellular Biology, Vol. 19, Issue 1
  • DOI: 10.1128/MCB.19.1.567

Biogenesis of telomerase ribonucleoproteins
journal, August 2012


Reconstitution and structural analysis of the yeast box H/ACA RNA-guided pseudouridine synthase
journal, November 2011


SHQ1 is required prior to NAF1 for assembly of H/ACA small nucleolar and telomerase RNPs
journal, April 2009


Stepwise RNP assembly at the site of H/ACA RNA transcription in human cells
journal, April 2006

  • Darzacq, Xavier; Kittur, Nupur; Roy, Sujayita
  • Journal of Cell Biology, Vol. 173, Issue 2
  • DOI: 10.1083/jcb.200601105

The Shq1p·Naf1p Complex Is Required for Box H/ACA Small Nucleolar Ribonucleoprotein Particle Biogenesis
journal, November 2002

  • Yang, Pok Kwan; Rotondo, Giuseppe; Porras, Tanya
  • Journal of Biological Chemistry, Vol. 277, Issue 47
  • DOI: 10.1074/jbc.M207669200

Crystal structure of an H/ACA box ribonucleoprotein particle
journal, August 2006


Dyskeratosis congenita: its link to telomerase and aplastic anaemia
journal, December 2003


X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions
journal, May 1998

  • Heiss, Nina S.; Knight, Stuart W.; Vulliamy, Tom J.
  • Nature Genetics, Vol. 19, Issue 1
  • DOI: 10.1038/ng0598-32

Dyskeratosis congenita
journal, May 2010


Advances in the understanding of dyskeratosis congenita
journal, April 2009


Disruption of telomerase trafficking by TCAB1 mutation causes dyskeratosis congenita
journal, January 2011

  • Zhong, F.; Savage, S. A.; Shkreli, M.
  • Genes & Development, Vol. 25, Issue 1
  • DOI: 10.1101/gad.2006411

The Box H/ACA RNP Assembly Factor Naf1p Contains a Domain Homologous to Gar1p Mediating its Interaction with Cbf5p
journal, August 2007

  • Leulliot, Nicolas; Godin, Katherine S.; Hoareau-Aveilla, Coralie
  • Journal of Molecular Biology, Vol. 371, Issue 5
  • DOI: 10.1016/j.jmb.2007.06.031

Mechanism of the AAA+ ATPases pontin and reptin in the biogenesis of H/ACA RNPs
journal, August 2012


Identification of ATPases Pontin and Reptin as Telomerase Components Essential for Holoenzyme Assembly
journal, March 2008


Structure and Functional Studies of the CS Domain of the Essential H/ACA Ribonucleoparticle Assembly Protein SHQ1
journal, November 2008

  • Singh, Mahavir; Gonzales, Fernando A.; Cascio, Duilio
  • Journal of Biological Chemistry, Vol. 284, Issue 3
  • DOI: 10.1074/jbc.M807337200

The Box H/ACA snoRNP Assembly Factor Shq1p is a Chaperone Protein Homologous to Hsp90 Cochaperones that Binds to the Cbf5p Enzyme
journal, July 2009

  • Godin, Katherine S.; Walbott, Hélène; Leulliot, Nicolas
  • Journal of Molecular Biology, Vol. 390, Issue 2
  • DOI: 10.1016/j.jmb.2009.04.076

The H/ACA RNP assembly factor SHQ1 functions as an RNA mimic
journal, November 2011

  • Walbott, H.; Machado-Pinilla, R.; Liger, D.
  • Genes & Development, Vol. 25, Issue 22
  • DOI: 10.1101/gad.176834.111

Pathogenic NAP57 mutations decrease ribonucleoprotein assembly in dyskeratosis congenita
journal, September 2009

  • Grozdanov, P. N.; Fernandez-Fuentes, N.; Fiser, A.
  • Human Molecular Genetics, Vol. 18, Issue 23
  • DOI: 10.1093/hmg/ddp416

The Box H/ACA Ribonucleoprotein Complex: Interplay of RNA and Protein Structures in Post-transcriptional RNA Modification
journal, November 2009

  • Hamma, Tomoko; Ferré-D'Amaré, Adrian R.
  • Journal of Biological Chemistry, Vol. 285, Issue 2
  • DOI: 10.1074/jbc.R109.076893

How a single protein complex accommodates many different H/ACA RNAs
journal, June 2006


Regulation of snoRNAs in Cancer: Close Encounters with Interferon
journal, April 2013

  • Nallar, Shreeram C.; Kalvakolanu, Dhananjaya V.
  • Journal of Interferon & Cytokine Research, Vol. 33, Issue 4
  • DOI: 10.1089/jir.2012.0106

Integrative Genomic Profiling of Human Prostate Cancer
journal, July 2010


New Views into the Prostate Cancer Genome
journal, July 2010


Identification of novel Notch target genes in T cell leukaemia
journal, January 2009

  • Chadwick, Nicholas; Zeef, Leo; Portillo, Virginia
  • Molecular Cancer, Vol. 8, Issue 1
  • DOI: 10.1186/1476-4598-8-35

Structural biology of the chaperone–usher pathway of pilus biogenesis
journal, October 2009

  • Waksman, Gabriel; Hultgren, Scott J.
  • Nature Reviews Microbiology, Vol. 7, Issue 11
  • DOI: 10.1038/nrmicro2220

SOFAST-HMQC Experiments for Recording Two-dimensional Deteronuclear Correlation Spectra of Proteins within a Few Seconds
journal, December 2005

  • Schanda, Paul; Kupče, Ēriks; Brutscher, Bernhard
  • Journal of Biomolecular NMR, Vol. 33, Issue 4
  • DOI: 10.1007/s10858-005-4425-x

The HADDOCK web server for data-driven biomolecular docking
journal, April 2010

  • de Vries, Sjoerd J.; van Dijk, Marc; Bonvin, Alexandre M. J. J.
  • Nature Protocols, Vol. 5, Issue 5
  • DOI: 10.1038/nprot.2010.32

WeNMR: Structural Biology on the Grid
journal, November 2012

  • Wassenaar, Tsjerk A.; van Dijk, Marc; Loureiro-Ferreira, Nuno
  • Journal of Grid Computing, Vol. 10, Issue 4
  • DOI: 10.1007/s10723-012-9246-z

Using Xplor-NIH for NMR Molecular Structure Determination
journal, October 2006

  • Schwieters, Charles D.; Kuszewski, John J.; Clore, G. Marius
  • ChemInform, Vol. 37, Issue 44
  • DOI: 10.1002/chin.200644278

The Xplor-NIH NMR molecular structure determination package
journal, January 2003


HKL2MAP : a graphical user interface for macromolecular phasing with SHELX programs
journal, September 2004


The CCP4 suite programs for protein crystallography
journal, September 1994


PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

Phaser crystallographic software
journal, July 2007

  • McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
  • Journal of Applied Crystallography, Vol. 40, Issue 4
  • DOI: 10.1107/S0021889807021206

Using chemical shift perturbation to characterise ligand binding
journal, August 2013


Measurement of Dipolar Couplings for Methylene and Methyl Sites in Weakly Oriented Macromolecules and Their Use in Structure Determination
journal, October 1998

  • Ottiger, Marcel; Delaglio, Frank; Marquardt, John L.
  • Journal of Magnetic Resonance, Vol. 134, Issue 2
  • DOI: 10.1006/jmre.1998.1546

TALOS+: a hybrid method for predicting protein backbone torsion angles from NMR chemical shifts
journal, June 2009

  • Shen, Yang; Delaglio, Frank; Cornilescu, Gabriel
  • Journal of Biomolecular NMR, Vol. 44, Issue 4
  • DOI: 10.1007/s10858-009-9333-z

AQUA and PROCHECK-NMR: Programs for checking the quality of protein structures solved by NMR
journal, December 1996

  • Laskowski, RomanA.; Rullmann, J. AntoonC.; MacArthur, MalcolmW.
  • Journal of Biomolecular NMR, Vol. 8, Issue 4
  • DOI: 10.1007/BF00228148

Works referencing / citing this record:

Telomerase Regulation from Beginning to the End
journal, September 2016

  • MacNeil, Deanna; Bensoussan, Hélène; Autexier, Chantal
  • Genes, Vol. 7, Issue 9
  • DOI: 10.3390/genes7090064

Solution structure of the P22S mutant of N-terminal CS domain of human Shq1
dataset, January 2015

  • Singh, Mahavir; Wang, Zhonghua; Cascio, Duilio
  • Biological Magnetic Resonance Bank
  • DOI: 10.13018/bmr19910

Assembly and trafficking of box C/D and H/ACA snoRNPs
journal, December 2016