Smoothing membrane protein structure determination by initial upstream stage improvements

Pedro, Ana; Queiroz, João A.; Passarinha, Luís A.

doi:10.1007/s00253-019-09873-1

Cited by 8 publications

(6 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The analysis presented here was made possible thanks to the evolving techniques of structure identification, which is difficult due to the nonaqueous environment excluding many experimental techniques [24][25][26][27][28]. Analyses are developed towards both the detailing [29] and generalization of protein structure [30].…”

Section: Discussionmentioning

confidence: 99%

Dependence of Protein Structure on Environment: FOD Model Applied to Membrane Proteins

Roterman

Stąpor

Gądek³

et al. 2021

Membranes

View full text Add to dashboard Cite

The natural environment of proteins is the polar aquatic environment and the hydrophobic (amphipathic) environment of the membrane. The fuzzy oil drop model (FOD) used to characterize water-soluble proteins, as well as its modified version FOD-M, enables a mathematical description of the presence and influence of diverse environments on protein structure. The present work characterized the structures of membrane proteins, including those that act as channels, and a water-soluble protein for contrast. The purpose of the analysis was to verify the possibility that an external force field can be used in the simulation of the protein-folding process, taking into account the diverse nature of the environment that guarantees a structure showing biological activity.

show abstract

Section: Discussionmentioning

confidence: 99%

Dependence of Protein Structure on Environment: FOD Model Applied to Membrane Proteins

Roterman

Stąpor

Gądek³

et al. 2021

Membranes

View full text Add to dashboard Cite

show abstract

“…Usually, the choice of a host is the first step to consider and depends on the type of protein being produced—namely, which eukaryotic systems are more suitable with regard to the need for extensive post-translational modifications. Moreover, the economic viability of the bioprocess is also highly dependent on the selected host [ 41 , 42 ]. E. coli and Pichia pastoris ( P. pastoris , currently reclassified as Komagataella pastoris ) microfactories are the most widely used hosts to obtain IFNs for clinical applications and with which to perform structural and functional studies.…”

Section: Therapeutic Cloned Interferonsmentioning

confidence: 99%

“…E. coli -based systems are often the preferred choice for recombinant proteins production, mostly due to the well-known advantages, such as the unparalleled fast growth kinetics (growth can double in about 20 min in appropriate conditions), easy manipulation, simple culture requirements, and cost-effectiveness [ 39 , 42 , 44 ]. Even though the recombinant protein production process can be a metabolic burden for the microorganism, causing a decrease in the generation time, high cell-density cultures can also be obtained using the host E. coli .…”

Section: Therapeutic Cloned Interferonsmentioning

confidence: 99%

“…The expression of proteins outside their original context can pose additional constraints since they might contain codons that are rarely used in the desired host or contain expression-limiting regulatory elements within their coding sequence [ 42 ]. In the case of IFN, this is particularly significant for its expression in E. coli since the presence of clusters AGG=AGA, CUA, AUA, GGA, or CCC codons in heterologous genes can decrease the quantity and quality of the heterologous protein [ 48 ].…”

Section: Therapeutic Cloned Interferonsmentioning

confidence: 99%

See 1 more Smart Citation

Interferon-Based Biopharmaceuticals: Overview on the Production, Purification, and Formulation

et al. 2021

View full text Add to dashboard Cite

The advent of biopharmaceuticals in modern medicine brought enormous benefits to the treatment of numerous human diseases and improved the well-being of many people worldwide. First introduced in the market in the early 1980s, the number of approved biopharmaceutical products has been steadily increasing, with therapeutic proteins, antibodies, and their derivatives accounting for most of the generated revenues. The success of pharmaceutical biotechnology is closely linked with remarkable developments in DNA recombinant technology, which has enabled the production of proteins with high specificity. Among promising biopharmaceuticals are interferons, first described by Isaacs and Lindenmann in 1957 and approved for clinical use in humans nearly thirty years later. Interferons are secreted autocrine and paracrine proteins, which by regulating several biochemical pathways have a spectrum of clinical effectiveness against viral infections, malignant diseases, and multiple sclerosis. Given their relevance and sustained market share, this review provides an overview on the evolution of interferon manufacture, comprising their production, purification, and formulation stages. Remarkable developments achieved in the last decades are herein discussed in three main sections: (i) an upstream stage, including genetically engineered genes, vectors, and hosts, and optimization of culture conditions (culture media, induction temperature, type and concentration of inducer, induction regimens, and scale); (ii) a downstream stage, focusing on single- and multiple-step chromatography, and emerging alternatives (e.g., aqueous two-phase systems); and (iii) formulation and delivery, providing an overview of improved bioactivities and extended half-lives and targeted delivery to the site of action. This review ends with an outlook and foreseeable prospects for underdeveloped aspects of biopharma research involving human interferons.

show abstract

“…Membrane proteins (MPs) constitute 20%–30% of all proteins encoded by the genome of various organisms 1 , 2 , 3 and represent the targets of most pharmacological agents. 4 , 5 , 6 MPs include signal transducers, channel proteins, metabolite transporters, cell surface receptors, enzymes, and anchors.…”

Section: Introductionmentioning

confidence: 99%

Application of polymersomes in membrane protein study and drug discovery: Progress, strategies, and perspectives

2022

Bioengineering & Transla Med

View full text Add to dashboard Cite

Membrane proteins (MPs) play key roles in cellular signaling pathways and are responsible for intercellular and intracellular interactions. Dysfunctional MPs are directly related to the pathogenesis of various diseases, and they have been exploited as one of the most sought‐after targets in the pharmaceutical industry. However, working with MPs is difficult given that their amphiphilic nature requires protection from biological membrane or membrane mimetics. Polymersomes are bilayered nano‐vesicles made of self‐assembled block copolymers that have been widely used as cell membrane mimetics for MP reconstitution and in engineering of artificial cells. This review highlights the prevailing trend in the application of polymersomes in MP study and drug discovery. We begin with a review on the techniques for synthesis and characterization of polymersomes as well as methods of MP insertion to form proteopolymersomes. Next, we review the structural and functional analysis of the different types of MPs reconstituted in polymersomes, including membrane transport proteins, MP complexes, and membrane receptors. We then summarize the factors affecting reconstitution efficiency and the quality of reconstituted MPs for structural and functional studies. Additionally, we discuss the potential in using proteopolymersomes as platforms for high‐throughput screening (HTS) in drug discovery to identify modulators of MPs. We conclude by providing future perspectives and recommendations on advancing the study of MPs and drug development using proteopolymersomes.

show abstract

Smoothing membrane protein structure determination by initial upstream stage improvements

Cited by 8 publications

References 115 publications

Dependence of Protein Structure on Environment: FOD Model Applied to Membrane Proteins

Dependence of Protein Structure on Environment: FOD Model Applied to Membrane Proteins

Interferon-Based Biopharmaceuticals: Overview on the Production, Purification, and Formulation

Application of polymersomes in membrane protein study and drug discovery: Progress, strategies, and perspectives

Contact Info

Product

Resources

About