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Protein Engineering: The Present and the Future 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biophysics".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 7524

Special Issue Editors


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Guest Editor
Department of Biochemistry and Molecular and Cell Biology, Institute for Biocomputation and Physics of Complex Systems (BIFI), University of Zaragoza, 50009 Zaragoza, Spain
Interests: protein stability; protein engineering; protein folding; biocomputation; drug discovery
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Guest Editor
Biochemical Sciences "Alessandro Rossi Fanelli", Sapienza Università di Roma, 00185 Rome, Italy
Interests: metabolic reprogramming in cancer cells ageing and neural diseases; metabolism of small dinucleotides involved in the formation of bacterial biofilm in chronic infections; role of nitric oxide and redox metabolism in bacterial pathogens and eukaryotic cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Proteins are simple polymers with extraordinary properties of enormous biological and economic value. They are widely used in biological catalysis, as key components of analytical methods, or as highly specific drugs for personalized medicine. Protein engineering uses synthetic methods that allow the application of rational physicochemical knowledge and the power of evolutionary approaches to the goal of creating, in useful quantities, novel proteins that exhibit advantageous properties. In some cases, the challenge is to stabilize a natural protein for cheaper production, easier transport and storage, and longer operational life. In others, completely new properties are sought, which requires a greater amount of design. Significant advances in the understanding of protein energetics, in computational methods for sequence and structural analysis, and in synthetic methods, combined with growing economic and social interest in proteins, claim the logical transformation of Protein Engineering into a predictive quantitative discipline, where success is guaranteed by good design. In this Special Issue we will show, with examples of their application to specific proteins, the most advanced methods that anticipate the transformation of Protein Engineering from an art for practitioners to a reliable technology.

Prof. Dr. Javier Sancho
Dr. Francesca Cutruzzola
Guest Editors

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Keywords

  • protein design
  • computational methods
  • evolutionary methods
  • protein stabilization
  • protein tailoring
  • industrial proteins
  • medicinal proteins

Published Papers (3 papers)

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Research

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25 pages, 6208 KiB  
Article
In Vitro and In Vivo Evidence towards Fibronectin’s Protective Effects against Prion Infection
by M. Carmen Garza, Sang-Gyun Kang, Chiye Kim, Eva Monleón, Jacques van der Merwe, David A. Kramer, Richard Fahlman, Valerie L. Sim, Judd Aiken, Debbie McKenzie, Leonardo M. Cortez and Holger Wille
Int. J. Mol. Sci. 2023, 24(24), 17525; https://doi.org/10.3390/ijms242417525 - 15 Dec 2023
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Abstract
A distinctive signature of the prion diseases is the accumulation of the pathogenic isoform of the prion protein, PrPSc, in the central nervous system of prion-affected humans and animals. PrPSc is also found in peripheral tissues, raising concerns about the [...] Read more.
A distinctive signature of the prion diseases is the accumulation of the pathogenic isoform of the prion protein, PrPSc, in the central nervous system of prion-affected humans and animals. PrPSc is also found in peripheral tissues, raising concerns about the potential transmission of pathogenic prions through human food supplies and posing a significant risk to public health. Although muscle tissues are considered to contain levels of low prion infectivity, it has been shown that myotubes in culture efficiently propagate PrPSc. Given the high consumption of muscle tissue, it is important to understand what factors could influence the establishment of a prion infection in muscle tissue. Here we used in vitro myotube cultures, differentiated from the C2C12 myoblast cell line (dC2C12), to identify factors affecting prion replication. A range of experimental conditions revealed that PrPSc is tightly associated with proteins found in the systemic extracellular matrix, mostly fibronectin (FN). The interaction of PrPSc with FN decreased prion infectivity, as determined by standard scrapie cell assay. Interestingly, the prion-resistant reserve cells in dC2C12 cultures displayed a FN-rich extracellular matrix while the prion-susceptible myotubes expressed FN at a low level. In agreement with the in vitro results, immunohistopathological analyses of tissues from sheep infected with natural scrapie demonstrated a prion susceptibility phenotype linked to an extracellular matrix with undetectable levels of FN. Conversely, PrPSc deposits were not observed in tissues expressing FN. These data indicate that extracellular FN may act as a natural barrier against prion replication and that the extracellular matrix composition may be a crucial feature determining prion tropism in different tissues. Full article
(This article belongs to the Special Issue Protein Engineering: The Present and the Future 2.0)
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Review

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60 pages, 4214 KiB  
Review
Engineering and Expression Strategies for Optimization of L-Asparaginase Development and Production
by Anastasiya N. Shishparenok, Yulia A. Gladilina and Dmitry D. Zhdanov
Int. J. Mol. Sci. 2023, 24(20), 15220; https://doi.org/10.3390/ijms242015220 - 16 Oct 2023
Cited by 1 | Viewed by 3307
Abstract
Genetic engineering for heterologous expression has advanced in recent years. Model systems such as Escherichia coli, Bacillus subtilis and Pichia pastoris are often used as host microorganisms for the enzymatic production of L-asparaginase, an enzyme widely used in the clinic for the [...] Read more.
Genetic engineering for heterologous expression has advanced in recent years. Model systems such as Escherichia coli, Bacillus subtilis and Pichia pastoris are often used as host microorganisms for the enzymatic production of L-asparaginase, an enzyme widely used in the clinic for the treatment of leukemia and in bakeries for the reduction of acrylamide. Newly developed recombinant L-asparaginase (L-ASNase) may have a low affinity for asparagine, reduced catalytic activity, low stability, and increased glutaminase activity or immunogenicity. Some successful commercial preparations of L-ASNase are now available. Therefore, obtaining novel L-ASNases with improved properties suitable for food or clinical applications remains a challenge. The combination of rational design and/or directed evolution and heterologous expression has been used to create enzymes with desired characteristics. Computer design, combined with other methods, could make it possible to generate mutant libraries of novel L-ASNases without costly and time-consuming efforts. In this review, we summarize the strategies and approaches for obtaining and developing L-ASNase with improved properties. Full article
(This article belongs to the Special Issue Protein Engineering: The Present and the Future 2.0)
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34 pages, 1483 KiB  
Review
Recombinant Protein Vaccines against Human Betacoronaviruses: Strategies, Approaches and Progress
by Angelina Kovalenko, Ekaterina Ryabchevskaya, Ekaterina Evtushenko, Nikolai Nikitin and Olga Karpova
Int. J. Mol. Sci. 2023, 24(2), 1701; https://doi.org/10.3390/ijms24021701 - 15 Jan 2023
Cited by 5 | Viewed by 2918
Abstract
Betacoronaviruses have already troubled humanity more than once. In 2002–2003 and 2012, the SARS-CoV and MERS-CoV, respectively, caused outbreaks of respiratory syndromes with a fatal outcome. The spread of the SARS-CoV-2 coronavirus has become a pandemic. These three coronaviruses belong to the genus [...] Read more.
Betacoronaviruses have already troubled humanity more than once. In 2002–2003 and 2012, the SARS-CoV and MERS-CoV, respectively, caused outbreaks of respiratory syndromes with a fatal outcome. The spread of the SARS-CoV-2 coronavirus has become a pandemic. These three coronaviruses belong to the genus Betacoronavirus and have a zoonotic origin. The emergence of new coronavirus infections in the future cannot be ruled out, and vaccination is the main way to prevent the spread of the infection. Previous experience in the development of vaccines against SARS and MERS has helped to develop a number of vaccines against SARS-CoV-2 in a fairly short time. Among them, there are quite a few recombinant protein vaccines, which seem to be very promising in terms of safety, minimization of side effects, storage and transportation conditions. The problem of developing a universal betacoronavirus vaccine is also still relevant. Here, we summarize the information on the designing of vaccines based on recombinant proteins against highly pathogenic human betacoronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2. Full article
(This article belongs to the Special Issue Protein Engineering: The Present and the Future 2.0)
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