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 Structural Basis for Specific Recognition of Rpt1p, an ATPase Subunit of 26 S Proteasome, by Proteasome-dedicated Chaperone Hsm3p

2012 ◽  
Vol 287 (15) ◽  
pp. 12172-12182 ◽  
Author(s):  
Kenji Takagi ◽  
Sangwoo Kim ◽  
Haruka Yukii ◽  
Mika Ueno ◽  
Ryo Morishita ◽  
...  
Keyword(s):  
Structural Model ◽  
Structural Basis ◽  
Hydrophobic Core ◽  
Atpase Subunit ◽  
Ubiquitinated Proteins ◽  
Terminal Domain ◽  
Ring Complex ◽  
Tetrameric Complex ◽  
Assembly Defect

The 26 S proteasome is a 2.5-MDa molecular machine that degrades ubiquitinated proteins in eukaryotic cells. It consists of a proteolytic core particle and two 19 S regulatory particles (RPs) composed of 6 ATPase (Rpt) and 13 non-ATPase (Rpn) subunits. Multiple proteasome-dedicated chaperones facilitate the assembly of the proteasome, but little is known about the detailed mechanisms. Hsm3, a 19 S RP dedicated chaperone, transiently binds to the C-terminal domain of the Rpt1 subunit and forms a tetrameric complex, Hsm3-Rpt1-Rpt2-Rpn1, during maturation of the ATPase ring of 19 S RP. To elucidate the structural basis of Hsm3 function, we determined the crystal structures of Hsm3 and its complex with the C-terminal domain of the Rpt1 subunit (Rpt1C). Hsm3 has a C-shaped structure that consists of 11 HEAT repeats. The structure of the Hsm3-Rpt1C complex revealed that the interacting surface between Hsm3 and Rpt1 is a hydrophobic core and a complementary charged surface. Mutations in the Hsm3-Rpt1 surface resulted in the assembly defect of the 26 S proteasome. Furthermore, a structural model of the Hsm3-Rpt ring complex and an in vitro binding assay suggest that Hsm3 can bind Rpt2 in addition to Rpt1. Collectively, our results provide the structural basis of the molecular functions of Hsm3 for the RP assembly.

scholarly journals Chloroplast Ribosomes Interact With the Insertase Alb3 in the Thylakoid Membrane

2021 ◽  
Vol 12 ◽  
Author(s):  
Bernd Ackermann ◽  
Beatrix Dünschede ◽  
Björn Pietzenuk ◽  
Bo Højen Justesen ◽  
Ute Krämer ◽  
...  
Keyword(s):  
Thylakoid Membrane ◽  
Molecular Mechanisms ◽  
Phylogenetic Analyses ◽  
Signal Recognition Particle ◽  
Ribosomal Subunit ◽  
Terminal Region ◽  
Hydrophobic Core ◽  
C Terminus ◽  
Terrestrial Life ◽  
Nascent Chain

Members of the Oxa1/YidC/Alb3 protein family are involved in the insertion, folding, and assembly of membrane proteins in mitochondria, bacteria, and chloroplasts. The thylakoid membrane protein Alb3 mediates the chloroplast signal recognition particle (cpSRP)-dependent posttranslational insertion of nuclear-encoded light harvesting chlorophyll a/b-binding proteins and participates in the biogenesis of plastid-encoded subunits of the photosynthetic complexes. These subunits are cotranslationally inserted into the thylakoid membrane, yet very little is known about the molecular mechanisms underlying docking of the ribosome-nascent chain complexes to the chloroplast SecY/Alb3 insertion machinery. Here, we show that nanodisc-embedded Alb3 interacts with ribosomes, while the homolog Alb4, also located in the thylakoid membrane, shows no ribosome binding. Alb3 contacts the ribosome with its C-terminal region and at least one additional binding site within its hydrophobic core region. Within the C-terminal region, two conserved motifs (motifs III and IV) are cooperatively required to enable the ribosome contact. Furthermore, our data suggest that the negatively charged C-terminus of the ribosomal subunit uL4c is involved in Alb3 binding. Phylogenetic analyses of uL4 demonstrate that this region newly evolved in the green lineage during the transition from aquatic to terrestrial life.

Solution structure and backbone dynamics for S1 domain of ribosomal protein S1 from Mycobacterium tuberculosis

2019 ◽  
Vol 48 (6) ◽  
pp. 491-501 ◽  
Author(s):  
Biling Huang ◽  
Shihui Fan ◽  
Yan Liu ◽  
Yufen Zhao ◽  
Donghai Lin ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Ribosomal Protein ◽  
Solution Structure ◽  
Backbone Dynamics ◽  
Ribosomal Protein S1

scholarly journals Structural Characterization of the Ribosome Maturation Protein, RimM

2007 ◽  
Vol 189 (17) ◽  
pp. 6397-6406 ◽  
Author(s):  
Sakura Suzuki ◽  
Ayako Tatsuguchi ◽  
Eiko Matsumoto ◽  
Masahito Kawazoe ◽  
Tatsuya Kaminishi ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Thermus Thermophilus ◽  
Ribosomal Subunit ◽  
Terminal Region ◽  
Resonance Spectroscopy ◽  
Structural Domain ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Wide Range ◽  
Ribosomal Protein S19

ABSTRACT The RimM protein has been implicated in the maturation of the 30S ribosomal subunit. It binds to ribosomal protein S19, located in the head domain of the 30S subunit. Multiple sequence alignments predicted that RimM possesses two domains in its N- and C-terminal regions. In the present study, we have produced Thermus thermophilus RimM in both the full-length form (162 residues) and its N-terminal fragment, spanning residues 1 to 85, as soluble proteins in Escherichia coli and have performed structural analyses by nuclear magnetic resonance spectroscopy. Residues 1 to 80 of the RimM protein fold into a single structural domain adopting a six-stranded β-barrel fold. On the other hand, the C-terminal region of RimM (residues 81 to 162) is partly folded in solution. Analyses of 1H-15N heteronuclear single quantum correlation spectra revealed that a wide range of residues in the C-terminal region, as well as the residues in the vicinity of a hydrophobic patch in the N-terminal domain, were dramatically affected upon complex formation with ribosomal protein S19.

Redox- and pH-linked conformational changes in triheme cytochrome PpcA from Geobacter sulfurreducens

2017 ◽  
Vol 474 (2) ◽  
pp. 231-246 ◽  
Author(s):  
Leonor Morgado ◽  
Marta Bruix ◽  
P. Raj Pokkuluri ◽  
Carlos A. Salgueiro ◽  
David L. Turner
Keyword(s):  
Conformational Changes ◽  
Solution Structure ◽  
Molecular Mechanisms ◽  
Three Dimensional ◽  
Axial Ligand ◽  
Geobacter Sulfurreducens ◽  
Cellular Growth ◽  
Dimensional Structure ◽  
Structural Basis ◽  
Natural Habitats

The periplasmic triheme cytochrome PpcA from Geobacter sulfurreducens is highly abundant; it is the likely reservoir of electrons to the outer surface to assist the reduction of extracellular terminal acceptors; these include insoluble metal oxides in natural habitats and electrode surfaces from which electricity can be harvested. A detailed thermodynamic characterization of PpcA showed that it has an important redox-Bohr effect that might implicate the protein in e−/H+ coupling mechanisms to sustain cellular growth. This functional mechanism requires control of both the redox state and the protonation state. In the present study, isotope-labeled PpcA was produced and the three-dimensional structure of PpcA in the oxidized form was determined by NMR. This is the first solution structure of a G. sulfurreducens cytochrome in the oxidized state. The comparison of oxidized and reduced structures revealed that the heme I axial ligand geometry changed and there were other significant changes in the segments near heme I. The pH-linked conformational rearrangements observed in the vicinity of the redox-Bohr center, both in the oxidized and reduced structures, constitute the structural basis for the differences observed in the pKa values of the redox-Bohr center, providing insights into the e−/H+ coupling molecular mechanisms driven by PpcA in G. sulfurreducens.

Solution structure of the ribosomal protein S19 from Thermus thermophilus 1 1Edited by P. E. Wright

1999 ◽  
Vol 292 (5) ◽  
pp. 1071-1081 ◽  
Author(s):  
Magnus Helgstrand ◽  
Alexey V Rak ◽  
Peter Allard ◽  
Natalia Davydova ◽  
Maria B Garber ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Solution Structure ◽  
Thermus Thermophilus ◽  
Ribosomal Protein S19

Combined Disruptions of the Ribosomal Protein s19 and Pim1 Kinase Genes Are Associated with Increased Myeloid/Erythroid Cellularity and Reduced Apoptosis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3097-3097
Author(s):  
Anne-Sophie Fröjmark ◽  
Jitendra Badhai ◽  
Jens Schuster ◽  
Joakim Klar ◽  
Maria Thuvesson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ribosomal Protein ◽  
Molecular Mechanisms ◽  
Bone Marrow Cells ◽  
Erythroid Progenitors ◽  
Pim1 Kinase ◽  
Cell Counts ◽  
Apoptotic Markers ◽  
Ribosomal Protein S19 ◽  
Marrow Cells

Abstract Diamond Blackfan anemia (DBA) is characterized by reduced proliferation and increased apoptosis of erythroid progenitors. Approximately 25% of patients are heterozygous for mutations in the gene encoding ribosomal protein S19 (RPS19). The molecular mechanisms behind DBA remain unclear and RPS19 was recently shown to interact with PIM1 kinase. To elucidate the phenotypic and cellular effects of this interaction we generated mice strains with the genotypes Rps19 +/− Pim1 +/+; Rps19 +/+ Pim1 −/− and Rps19 +/− Pim1 −/−. We analyzed the mice for peripheral blood and bone marrow parameters as well as apoptotic markers in primary bone marrow cells. The double mutant mice (Rps19 +/− Pim1 −/−) show normal growth and life span with increased white and red blood cell counts when compared to wild type, Rps19 heterozygous, and Pim1 null mice, respectively. Analysis of proteins in bone marrow cells shows that the combination of Rps19 insufficiency and Pim1 deficiency is associated with increased levels of Stat5 as well as the anti-apoptotic markers Mcl-1, Bcl-2 and Bcl-XL. The pro-apoptotic markers Bak, Caspase-3 and p21 show decreased levels whereas p53 remains unchanged. These findings suggest a co-operative effect of Rps19 insufficiency and Pim1 deficiency on cell proliferation in murine hematopoiesis.

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