scholarly journals Nuclear-mitotic apparatus protein: a structural protein interface between the nucleoskeleton and RNA splicing.

1994 ◽  
Vol 91 (4) ◽  
pp. 1505-1509 ◽  
Author(s):  
C. Zeng ◽  
D. He ◽  
S. M. Berget ◽  
B. R. Brinkley
Keyword(s):  
Rna Splicing ◽  
Protein A ◽  
Protein Interface ◽  
Structural Protein ◽  
Mitotic Apparatus ◽  
Nuclear Mitotic Apparatus

scholarly journals The Nuclear Mitotic Apparatus (NuMA) Protein: A Key Player for Nuclear Formation, Spindle Assembly, and Spindle Positioning

2021 ◽  
Vol 9 ◽  
Author(s):  
Tomomi Kiyomitsu ◽  
Susan Boerner
Keyword(s):  
Protein A ◽  
Spindle Assembly ◽  
Mitotic Cell ◽  
Cytoplasmic Dynein ◽  
Spindle Pole ◽  
Meiotic Spindle ◽  
Cell Cortex ◽  
Mitotic Apparatus ◽  
Spindle Positioning ◽  
Nuclear Mitotic Apparatus

The nuclear mitotic apparatus (NuMA) protein is well conserved in vertebrates, and dynamically changes its subcellular localization from the interphase nucleus to the mitotic/meiotic spindle poles and the mitotic cell cortex. At these locations, NuMA acts as a key structural hub in nuclear formation, spindle assembly, and mitotic spindle positioning, respectively. To achieve its variable functions, NuMA interacts with multiple factors, including DNA, microtubules, the plasma membrane, importins, and cytoplasmic dynein. The binding of NuMA to dynein via its N-terminal domain drives spindle pole focusing and spindle positioning, while multiple interactions through its C-terminal region define its subcellular localizations and functions. In addition, NuMA can self-assemble into high-ordered structures which likely contribute to spindle positioning and nuclear formation. In this review, we summarize recent advances in NuMA’s domains, functions and regulations, with a focus on human NuMA, to understand how and why vertebrate NuMA participates in these functions in comparison with invertebrate NuMA-related proteins.

scholarly journals Global Interactomics Connect Nuclear Mitotic Apparatus Protein NUMA1 to Influenza Virus Maturation

Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 731 ◽  
Author(s):  
Md Rahim ◽  
Ludger Klewes ◽  
Ali Zahedi-Amiri ◽  
Sabine Mai ◽  
Kevin Coombs
Keyword(s):  
Influenza A ◽  
Host Factors ◽  
Structural Proteins ◽  
Structural Protein ◽  
Host Proteins ◽  
Mitotic Apparatus ◽  
Multifunctional Protein ◽  
Virus Maturation ◽  
Infected Cells ◽  
Nuclear Mitotic Apparatus

Influenza A virus (IAV) infections remain a major human health threat. IAV has enormous genetic plasticity and can rapidly escape virus-targeted anti-viral strategies. Thus, there is increasing interest to identify host proteins and processes the virus requires for replication and maturation. The IAV non-structural protein 1 (NS1) is a critical multifunctional protein that is expressed to high levels in infected cells. Host proteins that interact with NS1 may serve as ideal targets for attenuating IAV replication. We previously developed and characterized broadly cross-reactive anti-NS1 monoclonal antibodies. For the current study, we used these mAbs to co-immunoprecipitate native IAV NS1 and interacting host proteins; 183 proteins were consistently identified in this NS1 interactome study, 124 of which have not been previously reported. RNAi screens identified 11 NS1-interacting host factors as vital for IAV replication. Knocking down one of these, nuclear mitotic apparatus protein 1 (NUMA1), dramatically reduced IAV replication. IAV genomic transcription and translation were not inhibited but transport of viral structural proteins to the cell membrane was hindered during maturation steps in NUMA1 knockdown (KD) cells.

Cell cycle-dependent SUMO-1 conjugation to nuclear mitotic apparatus protein (NuMA)

2014 ◽  
Vol 443 (1) ◽  
pp. 259-265 ◽  
Author(s):  
Jae Sung Seo ◽  
Ha Na Kim ◽  
Sun-Jick Kim ◽  
Jiyoung Bang ◽  
Eun-A Kim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mitotic Apparatus ◽  
Nuclear Mitotic Apparatus ◽  
Cycle Dependent

scholarly journals Suppression of conformational heterogeneity at a protein–protein interface

2015 ◽  
Vol 112 (29) ◽  
pp. 9028-9033 ◽  
Author(s):  
Lindsay N. Deis ◽  
Qinglin Wu ◽  
You Wang ◽  
Yang Qi ◽  
Kyle G. Daniels ◽  
...  
Keyword(s):  
Structural Changes ◽  
Tertiary Structure ◽  
Protein A ◽  
Side Chain ◽  
Host Immune System ◽  
Conformational Heterogeneity ◽  
Staphylococcal Protein A ◽  
Protein Interface ◽  
Multiple Binding ◽  
Important Virulence Factor

Staphylococcal protein A (SpA) is an important virulence factor from Staphylococcus aureus responsible for the bacterium’s evasion of the host immune system. SpA includes five small three-helix–bundle domains that can each bind with high affinity to many host proteins such as antibodies. The interaction between a SpA domain and the Fc fragment of IgG was partially elucidated previously in the crystal structure 1FC2. Although informative, the previous structure was not properly folded and left many substantial questions unanswered, such as a detailed description of the tertiary structure of SpA domains in complex with Fc and the structural changes that take place upon binding. Here we report the 2.3-Å structure of a fully folded SpA domain in complex with Fc. Our structure indicates that there are extensive structural rearrangements necessary for binding Fc, including a general reduction in SpA conformational heterogeneity, freezing out of polyrotameric interfacial residues, and displacement of a SpA side chain by an Fc side chain in a molecular-recognition pocket. Such a loss of conformational heterogeneity upon formation of the protein–protein interface may occur when SpA binds its multiple binding partners. Suppression of conformational heterogeneity may be an important structural paradigm in functionally plastic proteins.

scholarly journals The nuclear-mitotic apparatus protein is important in the establishment and maintenance of the bipolar mitotic spindle apparatus.

1992 ◽  
Vol 3 (11) ◽  
pp. 1259-1267 ◽  
Author(s):  
C H Yang ◽  
M Snyder
Keyword(s):  
Mitotic Spindle ◽  
Polar Regions ◽  
Mitotic Apparatus ◽  
Structural Support ◽  
Microtubule Motors ◽  
Interphase Cells ◽  
Spindle Apparatus ◽  
Nuclear Mitotic Apparatus ◽  
Multicellular Organisms ◽  
First Time

The formation and maintenance of the bipolar mitotic spindle apparatus require a complex and balanced interplay of several mechanisms, including the stabilization and separation of polar microtubules and the action of various microtubule motors. Nonmicrotubule elements are also present throughout the spindle apparatus and have been proposed to provide a structural support for the spindle. The Nuclear-Mitotic Apparatus protein (NuMA) is an abundant 240 kD protein that is present in the nucleus of interphase cells and concentrates in the polar regions of the spindle apparatus during mitosis. Sequence analysis indicates that NuMA possesses an unusually long alpha-helical central region characteristic of many filament forming proteins. In this report we demonstrate that microinjection of anti-NuMA antibodies into interphase and prophase cells results in a failure to form a mitotic spindle apparatus. Furthermore, injection of metaphase cells results in the collapse of the spindle apparatus into a monopolar microtubule array. These results identify for the first time a nontubulin component important for both the establishment and stabilization of the mitotic spindle apparatus in multicellular organisms. We suggest that nonmicrotubule structural components may be important for these processes.

scholarly journals The flexible C terminus of the rotavirus non-structural protein NSP4 is an important determinant of its biological properties

2008 ◽  
Vol 89 (6) ◽  
pp. 1485-1496 ◽  
Author(s):  
Deepa Rajasekaran ◽  
Narayan P. Sastri ◽  
Jagannath R. Marathahalli ◽  
Shanthinath S. Indi ◽  
Kiranmayee Pamidimukkala ◽  
...  
Keyword(s):  
Protein A ◽  
Biological Properties ◽  
Full Length ◽  
Structural Protein ◽  
Newborn Mice ◽  
Suckling Mice ◽  
C Terminus ◽  
Tht Fluorescence ◽  
Sequence Variations ◽  
Optimal Functions

The rotavirus non-structural protein NSP4 functions as the viral enterotoxin and intracellular receptor for the double-layered particles (DLP). The full-length protein cannot be expressed and/or purified to homogeneity from bacterial or insect cells. However, a bacterially expressed and purified mutant lacking the N-terminal 72 aa (ΔN72) was recently obtained from strains Hg18 and SA11 exhibiting approximately 17–20-, 150–200- and 13166–15800-fold lower DD50 (50% diarrhoea-inducing dose) values in suckling mice compared with that reported for the partially pure, full-length protein, a C-terminal M175I mutant and a synthetic peptide comprising aa 114–135, respectively, suggesting the requirement for a unique conformation for optimal functions of the purified protein. The stretch of approximately 40 aa from the C terminus of the cytoplasmic tail of the endoplasmic reticulum-anchored NSP4 is highly flexible and exhibits high sequence variation compared with the other regions, the significance of which in diarrhoea induction remain unresolved. Here, it was shown that every amino acid substitution or deletion in the flexible C terminus resulted in altered conformation, multimerization, trypsin resistance and thioflavin T (ThT) binding, and affected DLP binding and the diarrhoea-inducing ability of the highly diarrhoeagenic SA11 and Hg18 ΔN72 in suckling mice. These studies further revealed that high ThT fluorescence correlated with efficient diarrhoea induction, suggesting the importance of an optimal ThT-recognizable conformation in diarrhoea induction by purified NSP4. These results based on biological properties provide a possible conformational basis for understanding the influence of primary sequence variations on diarrhoea induction in newborn mice by purified NSP4s that cannot be explained by extensive sequence analyses.

scholarly journals The Interaction of Viperin with Hepatitis C Virus Non-Structural Protein 5A Inhibits the Catalytic Activity of Viperin

2019 ◽  
Author(s):  
Soumi Ghosh ◽  
Ayesha M. Patel ◽  
Timothy J. Grunkemeyer ◽  
Arti B. Dumbrepatil ◽  
Kelcie Zegalia ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Specific Activity ◽  
Regulatory Protein ◽  
Protein A ◽  
Structural Protein ◽  
Radical Sam ◽  
Replication Complex ◽  
Wide Range ◽  
Radical Sam Enzyme

AbstractThe radical SAM enzyme viperin exerts a wide range of antiviral effects through both the synthesis of the antiviral nucleotide 3’-deoxy-3’, 4’-didehydro-CTP (ddhCTP) and through its interactions with various cellular and viral proteins. Here we investigate the interaction of viperin with hepatitis C virus non-structural protein 5A (NS5A) and the host sterol regulatory protein, vesicle-associated membrane protein A (VAP-33). NS5A and VAP-33 form part of the viral replication complex that is essential for copying the RNA genome of the virus. Using transfected enzymes in HEK293T cells, we show that viperin binds to both NS5A and VAP-33 independently and that this interaction is dependent on all three proteins being localized to the ER membrane. Co-expression of viperin with VAP-33 and NS5A was found to reduce NS5A levels, most likely by increasing the rate of proteasomal degradation. However, co-expression of viperin with VAP-33 and NS5A also reduces the specific activity of viperin by ~ 3-fold. This observation suggests that NS5A may have evolved to bind viperin as a strategy to reduce ddhCTP synthesis, thereby reducing possibility of the replication complex introducing this chain-terminating nucleotide during genome synthesis.

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