Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Protein Solubility and Aggregation
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Protein Solubility and Aggregation

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 (31 December 2021) | Viewed by 10211

Special Issue Editor

Prof. Dr. Han S. Choe

E-Mail Website
Guest Editor
Department of Physiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul 05505, Republic of Korea
Interests: protein drug; structure modeling; cell therapy

Special Issue Information

Dear Colleagues,

Protein solubility and aggregation is a serious problem for protein sciences, pharmaceutical applications, and human health. The level of protein solubility ranges from almost completely insoluble to hundreds of milligrams per milliliter. Amino acids at the surface of a protein may determine the solubility. The structural stability of a protein may be important for solubility. Even a single amino acid mutation may change the solubility of a protein dramatically. External factors such as pH, ionic strength, temperature, mechanical stress, small molecules, etc. also affect the protein solubility. Low solubility would decrease the efficiency of the protein purification and the production yield of protein drugs. Protein aggregation, resulting from protein misfolding, leads to many diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and prion disease, to name but a few.

We invite researchers to contribute original and review articles regarding the protein solubility and aggregation. Potential topics include, but are not limited to the following:

  • Molecular mechanism of protein aggregation
  • Determinants of protein solubility 
  • Small molecule solubility enhancer
  • Chaperone protein
  • Database of protein solubility
  • Prediction of protein solubility
  • Protein aggregation disease
  • Protein misfolding
  • Therapeutics of protein aggregation

Prof. Dr. Han S. Choe
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

12 pages, 1401 KiB  
Article
Fusion Tag Design Influences Soluble Recombinant Protein Production in Escherichia coli
by Christoph Köppl, Nico Lingg, Andreas Fischer, Christina Kröß, Julian Loibl, Wolfgang Buchinger, Rainer Schneider, Alois Jungbauer, Gerald Striedner and Monika Cserjan-Puschmann
Int. J. Mol. Sci. 2022, 23(14), 7678; https://doi.org/10.3390/ijms23147678 - 12 Jul 2022
Cited by 12 | Viewed by 4089
Abstract
Fusion protein technologies to facilitate soluble expression, detection, or subsequent affinity purification in Escherichia coli are widely used but may also be associated with negative consequences. Although commonly employed solubility tags have a positive influence on titers, their large molecular mass inherently results [...] Read more.
Fusion protein technologies to facilitate soluble expression, detection, or subsequent affinity purification in Escherichia coli are widely used but may also be associated with negative consequences. Although commonly employed solubility tags have a positive influence on titers, their large molecular mass inherently results in stochiometric losses of product yield. Furthermore, the introduction of affinity tags, especially the polyhistidine tag, has been associated with undesirable changes in expression levels. Fusion tags are also known to influence the functionality of the protein of interest due to conformational changes. Therefore, particularly for biopharmaceutical applications, the removal of the fusion tag is a requirement to ensure the safety and efficacy of the therapeutic protein. The design of suitable fusion tags enabling the efficient manufacturing of the recombinant protein remains a challenge. Here, we evaluated several N-terminal fusion tag combinations and their influence on product titer and cell growth to find an ideal design for a generic fusion tag. For enhancing soluble expression, a negatively charged peptide tag derived from the T7 bacteriophage was combined with affinity tags and a caspase-2 cleavage site applicable for CASPase-based fusiON (CASPON) platform technology. The effects of each combinatorial tag element were investigated in an integrated manner using human fibroblast growth factor 2 as a model protein in fed-batch lab-scale bioreactor cultivations. To confirm the generic applicability for manufacturing, seven additional pharmaceutically relevant proteins were produced using the best performing tag of this study, named CASPON-tag, and tag removal was demonstrated. Full article
(This article belongs to the Special Issue Protein Solubility and Aggregation)
►▼ Show Figures

Figure 1

17 pages, 7436 KiB  
Article
Soluble Cytoplasmic Expression and Purification of Immunotoxin HER2(scFv)-PE24B as a Maltose Binding Protein Fusion
by Sangsu Park, Minh Quan Nguyen, Huynh Kim Khanh Ta, Minh Tan Nguyen, Gunsup Lee, Chong Jai Kim, Yeon Jin Jang and Han Choe
Int. J. Mol. Sci. 2021, 22(12), 6483; https://doi.org/10.3390/ijms22126483 - 17 Jun 2021
Cited by 14 | Viewed by 2797
Abstract
Human epidermal growth factor receptor 2 (HER-2) is overexpressed in many malignant tumors. The anti-HER2 antibody trastuzumab has been approved for treating HER2-positive early and metastatic breast cancers. Pseudomonas exotoxin A (PE), a bacterial toxin of Pseudomonas aeruginosa, consists of an A-domain [...] Read more.
Human epidermal growth factor receptor 2 (HER-2) is overexpressed in many malignant tumors. The anti-HER2 antibody trastuzumab has been approved for treating HER2-positive early and metastatic breast cancers. Pseudomonas exotoxin A (PE), a bacterial toxin of Pseudomonas aeruginosa, consists of an A-domain with enzymatic activity and a B-domain with cell binding activity. Recombinant immunotoxins comprising the HER2(scFv) single-chain Fv from trastuzumab and the PE24B catalytic fragment of PE display promising cytotoxic effects, but immunotoxins are typically insoluble when expressed in the cytoplasm of Escherichia coli, and thus they require solubilization and refolding. Herein, a recombinant immunotoxin gene was fused with maltose binding protein (MBP) and overexpressed in a soluble form in E. coli. Removal of the MBP yielded stable HER2(scFv)-PE24B at 91% purity; 0.25 mg of pure HER2(scFv)-PE24B was obtained from a 500 mL flask culture. Purified HER2(scFv)-PE24B was tested against four breast cancer cell lines differing in their surface HER2 level. The immunotoxin showed stronger cytotoxicity than HER2(scFv) or PE24B alone. The IC50 values for HER2(scFv)-PE24B were 28.1 ± 2.5 pM (n = 9) and 19 ± 1.4 pM (n = 9) for high HER2-positive cell lines SKBR3 and BT-474, respectively, but its cytotoxicity was lower against MDA-MB-231 and MCF7. Thus, fusion with MBP can facilitate the soluble expression and purification of scFv immunotoxins. Full article
(This article belongs to the Special Issue Protein Solubility and Aggregation)
►▼ Show Figures

Figure 1

18 pages, 2403 KiB  
Article
Solubility and Aggregation of Selected Proteins Interpreted on the Basis of Hydrophobicity Distribution
by Magdalena Ptak-Kaczor, Mateusz Banach, Katarzyna Stapor, Piotr Fabian, Leszek Konieczny and Irena Roterman
Int. J. Mol. Sci. 2021, 22(9), 5002; https://doi.org/10.3390/ijms22095002 - 08 May 2021
Cited by 9 | Viewed by 2417
Abstract
Protein solubility is based on the compatibility of the specific protein surface with the polar aquatic environment. The exposure of polar residues to the protein surface promotes the protein’s solubility in the polar environment. The aquatic environment also influences the folding process by [...] Read more.
Protein solubility is based on the compatibility of the specific protein surface with the polar aquatic environment. The exposure of polar residues to the protein surface promotes the protein’s solubility in the polar environment. The aquatic environment also influences the folding process by favoring the centralization of hydrophobic residues with the simultaneous exposure to polar residues. The degree of compatibility of the residue distribution, with the model of the concentration of hydrophobic residues in the center of the molecule, with the simultaneous exposure of polar residues is determined by the sequence of amino acids in the chain. The fuzzy oil drop model enables the quantification of the degree of compatibility of the hydrophobicity distribution observed in the protein to a form fully consistent with the Gaussian 3D function, which expresses an idealized distribution that meets the preferences of the polar water environment. The varied degrees of compatibility of the distribution observed with the idealized one allow the prediction of preferences to interactions with molecules of different polarity, including water molecules in particular. This paper analyzes a set of proteins with different levels of hydrophobicity distribution in the context of the solubility of a given protein and the possibility of complex formation. Full article
(This article belongs to the Special Issue Protein Solubility and Aggregation)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop