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

Journal Article · · Journal of Molecular Biology
 [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
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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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE; National Science Foundation (NSF)
Grant/Contract Number:
FC0302ER63421; AC02-06CH11357; P41 RR015301; P41 GM103403; MCB1022379; GM048123
OSTI ID:
1170018
Alternate ID(s):
OSTI ID: 1242546
Journal Information:
Journal of Molecular Biology, Vol. 427, Issue 4; ISSN 0022-2836
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 7 works
Citation information provided by
Web of Science

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Cited By (5)

Crystal structures of the naturally fused CS and cytochrome b 5 reductase ( b 5 R) domains of Ncb5or reveal an expanded CS fold, extensive CS– b 5 R interactions and productive binding of the NAD(P) + nicotinamide ring journal June 2019
Telomerase Regulation from Beginning to the End journal September 2016
Crystal structures of the naturally fused CS and cytochrome b 5 reductase ( b 5 R) domains of Ncb5or reveal an expanded CS fold, extensive CS– b 5 R interactions and productive binding of the NAD(P) + nicotinamide ring text January 2019
Solution structure of the P22S mutant of N-terminal CS domain of human Shq1 dataset January 2015
Assembly and trafficking of box C/D and H/ACA snoRNPs journal December 2016

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Related Subjects

60 APPLIED LIFE SCIENCES
NMR
chemical shift perturbation
X-ray crystal structure
dyskerin and Cbf5
telomerase