scholarly journals Molecular coevolution of nuclear and nucleolar localization signals inside basic domain of HIV-1 Tat

2021 ◽  
Author(s):  
Margarita A. Kurnaeva ◽  
Arthur O. Zalevsky ◽  
Eugene A. Arifulin ◽  
Olga M. Lisitsyna ◽  
Anna V. Tvorogova ◽  
...  
Keyword(s):  
Amino Acids ◽  
Viral Proteins ◽  
Nucleolar Localization ◽  
Functional Domains ◽  
Small Protein ◽  
Basic Domain ◽  
Protein Size ◽  
Charged Amino Acids ◽  
Hiv 1 ◽  
Positively Charged

During evolution, viruses had to adapt to an increasingly complex environment of eukaryotic cells. Viral proteins that need to enter the cell nucleus or associate with nucleoli possess nuclear localization signals (NLSs) and nucleolar localization signals (NoLSs) for nuclear and nucleolar accumulation, respectively. As viral proteins are relatively small, acquisition of novel sequences seems to be a more complicated task for viruses than for eukaryotes. Here, we carried out a comprehensive analysis of the basic domain (BD) of HIV-1 Tat to show how viral proteins might evolve with NLSs and NoLSs without an increase in protein size. The HIV-1 Tat BD is involved in several functions, the most important being the transactivation of viral transcription. The BD also functions as an NLS, although it is substantially longer than a typical NLS. It seems that different regions in the BD could function as NLSs due to its enrichment with positively charged amino acids. Additionally, the high positive net charge inevitably causes the BD to function as an NoLS through a charge-specific mechanism. The integration of NLSs and NoLSs into functional domains enriched with positively charged amino acids might be a mechanism that allows the condensation of different functional sequences in small protein regions and, as a result, to reduce protein size, influencing the origin and evolution of NLSs and NoLSs in viruses. IMPORTANCE Here, we investigated the molecular mechanism of NLS and NoLS integration into the basic domain of HIV-1 Tat ( 49 RKKRRQRRR 57 ), and found that these two supplementary functions (i.e., function of NLS and NoLS) are embedded in the basic domain amino acid sequence. The integration of NLSs and NoLSs into functional domains of viral proteins enriched with positively charged amino acids is a mechanism that allows the concentration of different functions within small protein regions. Integration of NLS and NoLS into functional protein domains might have influenced the viral evolution, as this could prevent an increase in the protein size.

scholarly journals Mechanisms and evolutionary implications of integration of different functions within HIV-1 Tat

2021 ◽  
Author(s):  
Margarita A. Kurnaeva ◽  
Arthur O. Zalevsky ◽  
Eugene A. Arifulin ◽  
Olga M. Lisitsyna ◽  
Anna V. Tvorogova ◽  
...  
Keyword(s):  
Amino Acids ◽  
Viral Proteins ◽  
Net Charge ◽  
Origin And Evolution ◽  
Nuclear Localization Signals ◽  
Protein Size ◽  
Charged Amino Acids ◽  
A Charge ◽  
Hiv 1 ◽  
Positively Charged

During evolution, viruses had to adapt to an increasingly complex environment of eukaryotic cells. Viral proteins that need to enter the cell nucleus or associate with nucleoli possess nuclear localization signals (NLSs) and nucleolar localization signals (NoLSs) for nuclear and nucleolar accumulation, respectively. As viral proteins are relatively small, acquisition of novel sequences seems to be a more complicated task for viruses than for eukaryotes. Here, we carried out a comprehensive analysis of the basic domain (BD) of HIV-1 Tat to show how viral proteins might evolve with NLSs and NoLSs without an increase in protein size. The HIV-1 Tat BD is involved in several functions, the most important being the transactivation of viral transcription. The BD also functions as an NLS, although it is substantially longer than a typical NLS. It seems that different regions in the BD could function as NLSs due to its enrichment with positively charged amino acids. Additionally, the high positive net charge inevitably causes the BD to function as an NoLS through a charge-specific mechanism. The integration of NLSs and NoLSs into functional domains enriched with positively charged amino acids might be a mechanism that allows the condensation of different functional sequences in small protein regions and, as a result, to reduce protein size, influencing the origin and evolution of NLSs and NoLSs in viruses.

scholarly journals The Superagonistic Activity of Bovine Thyroid-stimulating Hormone (TSH) and the Human TR1401 TSH Analog Is Determined by Specific Amino Acids in the Hinge Region of the Human TSH Receptor

2009 ◽  
Vol 284 (24) ◽  
pp. 16317-16324 ◽  
Author(s):  
Sandra Mueller ◽  
Gunnar Kleinau ◽  
Mariusz W. Szkudlinski ◽  
Holger Jaeschke ◽  
Gerd Krause ◽  
...  
Keyword(s):  
Amino Acids ◽  
Thyroid Stimulating Hormone ◽  
Hinge Region ◽  
Camp Production ◽  
Glycoprotein Hormone ◽  
Charged Amino Acids ◽  
Bovine Thyroid ◽  
Positively Charged ◽  
Bovine Tsh ◽  
Signaling Activity

Bovine TSH (bTSH) has a higher affinity to the human TSHR (hTSHR) and a higher signaling activity than human TSH (hTSH). The molecular reasons for these phenomena are unknown. Distinct negatively charged residues (Glu297, Glu303, and Asp382) in the hinge region of the hTSHR are known to be important for bTSH binding and signaling. To investigate the potential relevance of these positions for differences between bTSH and hTSH in the interaction to the hTSHR, we determined bTSH- and hTSH-mediated cAMP production of several substitutions at these three hinge residues. To examine specific variations of hTSH, we also investigated the superagonistic hTSH analog TR1401 (TR1401), whose sequence differs from hTSH by four additional positively charged amino acids that are also present in bTSH. To characterize possible interactions between the acidic hTSHR positions Glu297, Glu303, or Asp382 and the additional basic residues of TR1401, we investigated TR1401 binding and signaling properties. Our data reveal increased cAMP signaling of the hTSHR using TR1401 and bTSH compared with hTSH. Whereas Asp382 seems to be important for bTSH- and TR1401-mediated but not for hTSH-mediated signaling, the substitution E297K exhibits a decreased signaling for all three TSH variants. Interestingly, bTSH and TR1401 showed only a slightly different binding pattern. These observations imply that specific residues of the hinge region are mediators of the superagonistic activity of bTSH and TR1401 in contrast to hTSH. Moreover, the simultaneous localization of binding components in the glycoprotein hormone molecule and the receptor hinge region permits important reevaluation of interacting hormone receptor domains.

scholarly journals RNA-binding region of Macrobrachium rosenbergii nodavirus capsid protein

2014 ◽  
Vol 95 (9) ◽  
pp. 1919-1928 ◽  
Author(s):  
Zee Hong Goh ◽  
Nur Azmina Syakirin Mohd ◽  
Soon Guan Tan ◽  
Subha Bhassu ◽  
Wen Siang Tan
Keyword(s):  
Amino Acids ◽  
Capsid Protein ◽  
Rna Binding ◽  
Macrobrachium Rosenbergii ◽  
Freshwater Prawn ◽  
Internal Deletion ◽  
Binding Region ◽  
Rna Molecules ◽  
Charged Amino Acids ◽  
Positively Charged

White tail disease (WTD) kills prawn larvae and causes drastic losses to the freshwater prawn (Macrobrachium rosenbergii) industry. The main causative agent of WTD is Macrobrachium rosenbergii nodavirus (MrNV). The N-terminal end of the MrNV capsid protein is very rich in positively charged amino acids and is postulated to interact with RNA molecules. N-terminal and internal deletion mutagenesis revealed that the RNA-binding region is located at positions 20–29, where 80 % of amino acids are positively charged. Substitution of all these positively charged residues with alanine abolished the RNA binding. Mutants without the RNA-binding region still assembled into virus-like particles, suggesting that this region is not a part of the capsid assembly domain. This paper is, to the best of our knowledge, the first to report the specific RNA-binding region of MrNV capsid protein.

scholarly journals A Stretch of Positively Charged Amino Acids at the N Terminus ofHansenula polymorphaPex3p Is Involved in Incorporation of the Protein into the Peroxisomal Membrane

2000 ◽  
Vol 275 (14) ◽  
pp. 9986-9995 ◽  
Author(s):  
Richard J. S. Baerends ◽  
Klaas Nico Faber ◽  
Anita M. Kram ◽  
Jan A. K. W. Kiel ◽  
Ida J. van der Klei ◽  
...  
Keyword(s):  
Amino Acids ◽  
Peroxisomal Membrane ◽  
Charged Amino Acids ◽  
N Terminus ◽  
Positively Charged

Study of R-group positively charged amino acids' UV

2009 ◽  
Author(s):  
Teng fei Tian ◽  
Gui zhong Liu ◽  
Xian hui Meng ◽  
Xiao qian Tan ◽  
Yong liang Liu
Keyword(s):  
Amino Acids ◽  
Charged Amino Acids ◽  
Positively Charged

Tetraphenyl porphyrin films as selective detectors for amino acid molecules

2020 ◽  
Vol 24 (10) ◽  
pp. 1215-1223
Author(s):  
Jesús Miguel Rivera ◽  
Margarita Rivera
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Quartz Crystal Microbalance ◽  
Quartz Crystal ◽  
Binding Energies ◽  
Charged Amino Acids ◽  
Tetraphenyl Porphyrin ◽  
Pseudo Second Order ◽  
Selective Detectors ◽  
Positively Charged

The interaction of different amino acids and vacuum evaporated tetraphenyl porphyrin films was investigated by using kinetic isotherms, UV-vis spectroscopy, quartz crystal microbalance and density functional theory techniques. The adsorption process was analyzed by using pseudo-first-order and pseudo-second-order models. From these results, the adsorption order changed depending on the chemical characteristics of the porphyrin film, although most of the interactions were classified as pseudo-second-order at the films interface. From absorbance measurements, red shifts on the Soret peak positions were observed for all amino acids interacting with the metal free and the ZnTPP systems, while the position of the Soret peak barely change for the CuTPP surface, except for a slight bathocromic shift for arginine. On the other hand, the broadening of the Soret peak was more important for the ZnTPP and H2TPP surfaces, but the interaction with the CuTPP interfaces decreased the width of the peaks in all cases. In addition, a quartz crystal microbalance analysis was employed to investigate the film sensing performance during amino acid exposure. From these results, positively charged amino acids were more easily adsorbed on the films in contrast with the polar (serine) molecule. DFT calculations exhibited important deformations for H2TPP, the out-of-plane displacement of the Zn atom for ZnTPP, and hydrogen bond interactions with the CuTPP molecule. DFT also showed high binding energies for the positively charged amino acids but low binding energies for serine in agreement with experimental data. From these results, porphyrin films could be used as selective detectors for various L-amino acid molecules.

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