Analysis of the interactome of ribosomal protein S19 mutants

PROTEOMICS ◽  
2014 ◽  
Vol 14 (20) ◽  
pp. 2286-2296 ◽  
Author(s):  
Marianna Caterino ◽  
Anna Aspesi ◽  
Elisa Pavesi ◽  
Esther Imperlini ◽  
Daniela Pagnozzi ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Ribosomal Protein S19

scholarly journals Structural Basis for the C-Terminal Domain of Mycobacterium tuberculosis Ribosome Maturation Factor RimM to Bind Ribosomal Protein S19

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 597
Author(s):  
Haoran Zhang ◽  
Qiuxiang Zhou ◽  
Chenyun Guo ◽  
Liubin Feng ◽  
Huilin Wang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Ribosomal Protein ◽  
Solution Structure ◽  
Molecular Mechanisms ◽  
Structural Model ◽  
Ribosomal Subunit ◽  
Structural Basis ◽  
Hydrophobic Core ◽  
Terminal Domain ◽  
Ribosomal Protein S19

Multidrug-resistant tuberculosis (TB) is a serious threat to public health, calling for the development of new anti-TB drugs. Chaperon protein RimM, involved in the assembly of ribosomal protein S19 into 30S ribosomal subunit during ribosome maturation, is a potential drug target for TB treatment. The C-terminal domain (CTD) of RimM is primarily responsible for binding S19. However, both the CTD structure of RimM from Mycobacterium tuberculosis (MtbRimMCTD) and the molecular mechanisms underlying MtbRimMCTD binding S19 remain elusive. Here, we report the solution structure, dynamics features of MtbRimMCTD, and its interaction with S19. MtbRimMCTD has a rigid hydrophobic core comprised of a relatively conservative six-strand β-barrel, tailed with a short α-helix and interspersed with flexible loops. Using several biophysical techniques including surface plasmon resonance (SPR) affinity assays, nuclear magnetic resonance (NMR) assays, and molecular docking, we established a structural model of the MtbRimMCTD–S19 complex and indicated that the β4-β5 loop and two nonconserved key residues (D105 and H129) significantly contributed to the unique pattern of MtbRimMCTD binding S19, which might be implicated in a form of orthogonality for species-dependent RimM–S19 interaction. Our study provides the structural basis for MtbRimMCTD binding S19 and is beneficial to the further exploration of MtbRimM as a potential target for the development of new anti-TB drugs.

scholarly journals Mice with ribosomal protein S19 deficiency develop bone marrow failure and symptoms like patients with Diamond-Blackfan anemia

Blood ◽  
2011 ◽  
Vol 118 (23) ◽  
pp. 6087-6096 ◽  
Author(s):  
Pekka Jaako ◽  
Johan Flygare ◽  
Karin Olsson ◽  
Ronan Quere ◽  
Mats Ehinger ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Rna Interference ◽  
Ribosomal Protein ◽  
Mouse Models ◽  
Bone Marrow Failure ◽  
Macrocytic Anemia ◽  
Down Regulation ◽  
Hematopoietic Stem ◽  
Diamond Blackfan Anemia ◽  
Ribosomal Protein S19

Abstract Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by a functional haploinsufficiency of genes encoding for ribosomal proteins. Among these genes, ribosomal protein S19 (RPS19) is mutated most frequently. Generation of animal models for diseases like DBA is challenging because the phenotype is highly dependent on the level of RPS19 down-regulation. We report the generation of mouse models for RPS19-deficient DBA using transgenic RNA interference that allows an inducible and graded down-regulation of Rps19. Rps19-deficient mice develop a macrocytic anemia together with leukocytopenia and variable platelet count that with time leads to the exhaustion of hematopoietic stem cells and bone marrow failure. Both RPS19 gene transfer and the loss of p53 rescue the DBA phenotype implying the potential of the models for testing novel therapies. This study demonstrates the feasibility of transgenic RNA interference to generate mouse models for human diseases caused by haploinsufficient expression of a gene.

scholarly journals The 5' untranslated region of mRNA for ribosomal protein S19 is involved in its translational regulation during Xenopus development.

1990 ◽  
Vol 10 (2) ◽  
pp. 816-822 ◽  
Author(s):  
P Mariottini ◽  
F Amaldi
Keyword(s):  
Ribosomal Protein ◽  
Untranslated Region ◽  
Ribosomal Proteins ◽  
Translational Regulation ◽  
Xenopus Development ◽  
Untranslated Sequence ◽  
Gene Coding ◽  
Ribosomal Protein S19 ◽  
Fused Gene

During Xenopus development, the synthesis of ribosomal proteins is regulated at the translational level. To identify the region of the ribosomal protein mRNAs responsible for their typical translational behavior, we constructed a fused gene in which the upstream sequences (promoter) and the 5' untranslated sequence (first exon) of the gene coding for Xenopus ribosomal protein S19 were joined to the coding portion of the procaryotic chloramphenicol acetyltransferase (CAT) gene deleted of its own 5' untranslated region. This fused gene was introduced in vivo by microinjection into Xenopus fertilized eggs, and its activity was monitored during embryogenesis. By analyzing the pattern of appearance of CAT activity and the distribution of the S19-CAT mRNA between polysomes and messenger ribonucleoproteins, it was concluded that the 35-nucleotide-long 5' untranslated region of the S19 mRNA is able to confer to the fused S19-CAT mRNA the translational behavior typical of ribosomal proteins during Xenopus embryo development.

The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia

10.1038/5951 ◽  
1999 ◽  
Vol 21 (2) ◽  
pp. 169-175 ◽  
Author(s):  
Natalia Draptchinskaia ◽  
Peter Gustavsson ◽  
Björn Andersson ◽  
Monica Pettersson ◽  
Thiébaut-Noël Willig ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Gene Encoding ◽  
Ribosomal Protein S19 ◽  
Diamond Blackfan Anaemia

Preliminary NMR studies of Thermus thermophilus ribosomal protein S19 overproduced in Escherichia coli

FEBS Letters ◽  
1997 ◽  
Vol 415 (2) ◽  
pp. 155-159 ◽  
Author(s):  
Natalia L Davydova ◽  
Alexey V Rak ◽  
Olga I Gryaznova ◽  
Anders Liljas ◽  
Bengt-Harald Jonsson ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Ribosomal Protein ◽  
Thermus Thermophilus ◽  
Nmr Studies ◽  
Ribosomal Protein S19

scholarly journals Regulation of erythropoiesis in zebrafish model by the kinase of ribosomal protein S19

2020 ◽  
Vol 93 (0) ◽  
pp. 3-P-336
Author(s):  
Hidetsugu Torihara ◽  
Sayomi Nakamine-Higa ◽  
Shiho Okitsu ◽  
Hideyuki Yamamoto
Keyword(s):  
Ribosomal Protein ◽  
Zebrafish Model ◽  
Ribosomal Protein S19

scholarly journals Daptomycin, a last-resort antibiotic, binds ribosomal protein S19 in humans

2016 ◽  
Vol 15 (1) ◽  
Author(s):  
Michael P. Gotsbacher ◽  
Sungmin Cho ◽  
Ho Jeong Kwon ◽  
Peter Karuso
Keyword(s):  
Ribosomal Protein ◽  
Ribosomal Protein S19

scholarly journals Targeted Disruption of the Ribosomal Protein S19 Gene Is Lethal Prior to Implantation

2004 ◽  
Vol 24 (9) ◽  
pp. 4032-4037 ◽  
Author(s):  
Hans Matsson ◽  
Edward J. Davey ◽  
Natalia Draptchinskaia ◽  
Isao Hamaguchi ◽  
Andreas Ooka ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Ribosomal Proteins ◽  
Normal Growth ◽  
Lethal Effect ◽  
Blastocyst Stage ◽  
Targeted Disruption ◽  
Gene Encoding ◽  
Diamond Blackfan Anemia ◽  
Associated Malformations ◽  
Ribosomal Protein S19

ABSTRACT The ribosomal protein S19 (RPS19) is located in the small (40S) subunit and is one of 79 ribosomal proteins. The gene encoding RPS19 is mutated in approximately 25% of patients with Diamond-Blackfan anemia, which is a rare congenital erythroblastopenia. Affected individuals present with decreased numbers or the absence of erythroid precursors in the bone marrow, and associated malformations of various organs are common. We produced C57BL/6J mice with a targeted disruption of murine Rps19 to study its role in erythropoiesis and development. Mice homozygous for the disrupted Rps19 were not identified as early as the blastocyst stage, indicating a lethal effect. In contrast, mice heterozygous for the disrupted Rps19 allele have normal growth and organ development, including that of the hematopoietic system. Our findings indicate that zygotes which are Rps19 −/− do not form blastocysts, whereas one normal Rps19 allele in C57BL/6J mice is sufficient to maintain normal ribosomal and possibly extraribosomal functions.

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