Why there is more to protein evolution than protein function: splicing, nucleosomes and dual-coding sequence

2009 ◽  
Vol 37 (4) ◽  
pp. 756-761 ◽  
Author(s):  
Tobias Warnecke ◽  
Claudia C. Weber ◽  
Laurence D. Hurst
Keyword(s):  
Amino Acid ◽  
Protein Evolution ◽  
Protein Function ◽  
Dual Coding ◽  
Splice Enhancer ◽  
Dna And Rna ◽  
Rates Of Evolution ◽  
Exonic Splice ◽  
Production History

There is considerable variation in the rate at which different proteins evolve. Why is this? Classically, it has been considered that the density of functionally important sites must predict rates of protein evolution. Likewise, amino acid choice is usually assumed to reflect optimal protein function. In the present article, we briefly review evidence suggesting that this protein function-centred view is too simplistic. In particular, we concentrate on how selection acting during the protein's production history can also affect protein evolutionary rates and amino acid choice. Exploring the role of selection at the DNA and RNA level, we specifically address how the need (i) to specify exonic splice enhancer motifs in pre-mRNA, and (ii) to ensure nucleosome positioning on DNA have an impact on amino acid choice and rates of evolution. For both, we review evidence that sequence affected by more than one coding demand is particularly constrained. Strikingly, in mammals, splicing-related constraints are quantitatively as important as expression parameters in predicting rates of protein evolution. These results indicate that there is substantially more to protein evolution than protein functional constraints.

scholarly journals Aggregation is a Context-Dependent Constraint on Protein Evolution

2021 ◽  
Vol 8 ◽  
Author(s):  
Michele Monti ◽  
Alexandros Armaos ◽  
Marco Fantini ◽  
Annalisa Pastore ◽  
Gian Gaetano Tartaglia
Keyword(s):  
Molecular Evolution ◽  
Protein Evolution ◽  
Protein Function ◽  
Beta Lactamase ◽  
Data Set ◽  
Cellular Processes ◽  
Bacterial Enzyme ◽  
Rna Biogenesis ◽  
Context Dependent

Solubility is a requirement for many cellular processes. Loss of solubility and aggregation can lead to the partial or complete abrogation of protein function. Thus, understanding the relationship between protein evolution and aggregation is an important goal. Here, we analysed two deep mutational scanning experiments to investigate the role of protein aggregation in molecular evolution. In one data set, mutants of a protein involved in RNA biogenesis and processing, human TAR DNA binding protein 43 (TDP-43), were expressed in S. cerevisiae. In the other data set, mutants of a bacterial enzyme that controls resistance to penicillins and cephalosporins, TEM-1 beta-lactamase, were expressed in E. coli under the selective pressure of an antibiotic treatment. We found that aggregation differentiates the effects of mutations in the two different cellular contexts. Specifically, aggregation was found to be associated with increased cell fitness in the case of TDP-43 mutations, as it protects the host from aberrant interactions. By contrast, in the case of TEM-1 beta-lactamase mutations, aggregation is linked to a decreased cell fitness due to inactivation of protein function. Our study shows that aggregation is an important context-dependent constraint of molecular evolution and opens up new avenues to investigate the role of aggregation in the cell.

The role of active-site amino acid residues in the cleavage of DNA and RNA substrates by human apurinic/apyrimidinic endonuclease APE1

2020 ◽  
Vol 1864 (12) ◽  
pp. 129718
Author(s):  
I.V. Alekseeva ◽  
A.A. Kuznetsova ◽  
A.S. Bakman ◽  
O.S. Fedorova ◽  
N.A. Kuznetsov
Keyword(s):  
Amino Acid ◽  
Active Site ◽  
Amino Acid Residues ◽  
Dna And Rna

scholarly journals A unique exonic splice enhancer mutation in a family with X-linked mental retardation and epilepsy points to a novel role of the renin receptor

2005 ◽  
Vol 14 (8) ◽  
pp. 1019-1027 ◽  
Author(s):  
Juliane Ramser ◽  
Fatima E. Abidi ◽  
Celine A. Burckle ◽  
Claus Lenski ◽  
Helga Toriello ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Exonic Splice Enhancer ◽  
Splice Enhancer ◽  
Exonic Splice

scholarly journals The evolution and engineering of enzyme activity through tuning conformational landscapes

2021 ◽  
Vol 34 ◽  
Author(s):  
Adam M Damry ◽  
Colin J Jackson
Keyword(s):  
Structural Biology ◽  
Protein Evolution ◽  
Protein Function ◽  
Conformational Sampling ◽  
Conformational Substates ◽  
Evolutionary Trajectories ◽  
Conformational Landscape ◽  
Enzyme Functions ◽  
Insight Into

Abstract Proteins are dynamic molecules whose structures consist of an ensemble of conformational states. Dynamics contribute to protein function and a link to protein evolution has begun to emerge. This increased appreciation for the evolutionary impact of conformational sampling has grown from our developing structural biology capabilities and the exploration of directed evolution approaches, which have allowed evolutionary trajectories to be mapped. Recent studies have provided empirical examples of how proteins can evolve via conformational landscape alterations. Moreover, minor conformational substates have been shown to be involved in the emergence of new enzyme functions as they can become enriched through evolution. The role of remote mutations in stabilizing new active site geometries has also granted insight into the molecular basis underpinning poorly understood epistatic effects that guide protein evolution. Finally, we discuss how the growth of our understanding of remote mutations is beginning to refine our approach to engineering enzymes.

scholarly journals Aggregation is a context-dependent constraint on protein evolution

2021 ◽  
Author(s):  
Michele Monti ◽  
Alexandros Armaos ◽  
Marco Fantini ◽  
Annalisa Pastore ◽  
Gian Gaetano Tartaglia
Keyword(s):  
Protein Evolution ◽  
Protein Function ◽  
Beta Lactamase ◽  
Data Set ◽  
Cellular Processes ◽  
Bacterial Enzyme ◽  
Rna Biogenesis ◽  
Context Dependent ◽  
The Relationship

Solubility is a requirement for many cellular processes. Loss of solubility and aggregation can lead to the partial or complete abrogation of protein function. Thus, understanding the relationship between protein evolution and aggregation is an important goal. Here, we analysed two deep mutational scanning experiments to investigate the role of protein aggregation in molecular evolution.In one data set, mutants of a protein involved in RNA biogenesis and processing, human TAR DNA binding protein 43 (TDP-43), were expressed inS. cerevisiae. In the other data set, mutants of a bacterial enzyme that controls resistance to penicillins and cephalosporins, TEM-1 beta-lactamase, were expressed inE. coli under the selective pressure of an antibiotic treatment. We found that aggregation differentiates the effects of mutations in the two different cellular contexts. Specifically, aggregation was found to be associated with increased cell fitness in the case of TDP-43 mutations, as it protects the host from aberrant interactions. By contrast, in the case of TEM-1 beta-lactamase mutations, aggregation is linked to a decreased cell fitness due to inactivation of protein function.Our study shows that aggregation is an important context-dependent constraint of molecular evolution and opens up new avenues to investigate the role of aggregation in different cellular contexts-

Transcription factor IIIA (TFIIIA) in the second decade

1996 ◽  
Vol 109 (3) ◽  
pp. 535-539 ◽  
Author(s):  
B.S. Shastry
Keyword(s):  
Transcription Factor ◽  
Amino Acid ◽  
Amino Acid Residue ◽  
Rna Binding ◽  
Current Knowledge ◽  
Zinc Fingers ◽  
Specific Factor ◽  
Transcription Factor Iiia ◽  
Dna And Rna

Transcription factor IIIA is a very extensively studied eukaryotic gene specific factor. It is a special member of the zinc finger family of nucleic acid binding proteins with multiple functions. Its N-terminal polypeptide (280 amino acid residue containing peptide; finger containing region) carries out sequence specific DNA and RNA binding and the C-terminal peptide (65 amino acid residue containing peptide; non-finger region) is involved in the transactivation process possibly by interacting with other general factors. It is a unique factor in the sense that it binds to two structurally different nucleic acids, DNA and RNA. It accomplishes this function through its zinc fingers, which are arranged into a cluster of nine motifs. Over the past three years there has been considerable interest in determining the structural features of zinc fingers, identifying the fingers that preferentially recognize DNA and RNA, defining the role of metal binding ligands and the linker region in promotor recognition and the role of C-terminal amino acid sequence in the gene activation. This article briefly reviews our current knowledge on this special protein in these areas.

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