Solubility and Aggregation of Selected Proteins Interpreted on the Basis of Hydrophobicity Distribution

Ptak-Kaczor, Magdalena; Banach, Mateusz; Stąpor, Katarzyna; Fabian, Piotr; Konieczny, Leszek; Roterman, Irena

doi:10.3390/ijms22095002

Cited by 12 publications

(14 citation statements)

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“…The subdomain and the connecting α-helix also support an ability to carry very large lipid loads. We note, however, that the expansion of the hydrophobic core of a lipid binding cavity can result in a less soluble surface ( Biterova et al, 2019 ; Ptak-Kaczor et al, 2021 ). In this context, we propose that the C-terminal region provides a cover that increases the solubility of Vg, possibly shifting deeper into the cavity in response to increasing loads.…”

Section: Expansion and Compressionmentioning

confidence: 85%

How Honey Bee Vitellogenin Holds Lipid Cargo: A Role for the C-Terminal

Leipart¹,

Halskau²,

Amdam

2022

Front. Mol. Biosci.

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Vitellogenin (Vg) is a phylogenetically broad glycolipophosphoprotein. A major function of this protein is holding lipid cargo for storage and transportation. Vg has been extensively studied in honey bees (Apis mellifera) due to additional functions in social traits. Using AlphaFold and EM contour mapping, we recently described the protein structure of honey bee Vg. The full-length protein structure reveals a large hydrophobic lipid binding site and a well-defined fold at the C-terminal region. Now, we outline a shielding mechanism that allows the C-terminal region of Vg to cover a large hydrophobic area exposed in the all-atom model. We propose that this C-terminal movement influences lipid molecules’ uptake, transport, and delivery. The mechanism requires elasticity in the Vg lipid core as described for homologous proteins in the large lipid transfer protein (LLTP) superfamily to which Vg belongs. Honey bee Vg has, additionally, several structural arrangements that we interpret as beneficial for the functional flexibility of the C-terminal region. The mechanism proposed here may be relevant for the Vg molecules of many species.

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Section: Expansion and Compressionmentioning

confidence: 85%

How Honey Bee Vitellogenin Holds Lipid Cargo: A Role for the C-Terminal

Leipart¹,

Halskau²,

Amdam

2022

Front. Mol. Biosci.

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“…The vector is shown in black, and the vaccine DNA sequence is highlighted in red. The DNA sequence is typically inserted in the MCS between the BamH1 and Xho1 cutting sites it affects heterologous overexpression of proteins, formulation of products, and their stability [58]. The solubility of vaccine protein overexpressed in E. coli is an important criterion for many biochemical and functional analyses.…”

Section: Discussionmentioning

confidence: 99%

A novel strategy for developing vaccine candidate against Jaagsiekte sheep retrovirus from the envelope and gag proteins: an in-silico approach

2022

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Background Sheep pulmonary adenocarcinoma (OPA) is a contagious lung cancer of sheep caused by the Jaagsiekte retrovirus (JSRV). OPA typically has a serious economic impact worldwide. A vaccine has yet to be developed, even though the disease has been globally spread, along with its complications. This study aimed to construct an effective multi-epitopes vaccine against JSRV eliciting B and T lymphocytes using immunoinformatics tools. Results The designed vaccine was composed of 499 amino acids. Before the vaccine was computationally validated, all critical parameters were taken into consideration; including antigenicity, allergenicity, toxicity, and stability. The physiochemical properties of the vaccine displayed an isoelectric point of 9.88. According to the Instability Index (II), the vaccine was stable at 28.28. The vaccine scored 56.51 on the aliphatic index and -0.731 on the GRAVY, indicating that the vaccine was hydrophilic. The RaptorX server was used to predict the vaccine's tertiary structure, the GalaxyWEB server refined the structure, and the Ramachandran plot and the ProSA-web server validated the vaccine's tertiary structure. Protein-sol and the SOLPro servers showed the solubility of the vaccine. Moreover, the high mobile regions in the vaccine’s structure were reduced and the vaccine’s stability was improved by disulfide engineering. Also, the vaccine construct was docked with an ovine MHC-1 allele and showed efficient binding energy. Immune simulation remarkably showed high levels of immunoglobulins, T lymphocytes, and INF-γ secretions. The molecular dynamic simulation provided the stability of the constructed vaccine. Finally, the vaccine was back-transcribed into a DNA sequence and cloned into a pET-30a ( +) vector to affirm the potency of translation and microbial expression. Conclusion A novel multi-epitopes vaccine construct against JSRV, was formed from B and T lymphocytes epitopes, and was produced with potential protection. This study might help in controlling and eradicating OPA.

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“…A detailed analysis of the immunological domains and their specificity presented in [ 102 ] indicates a specific adaptation of the V domains to the function performed. Similarly, transthyretin also shows a local, well-defined, specific mismatch in the distribution of T and O [ 103 , 104 , 105 ]. The amyloid transformation associated with a significant increase in the value of the K parameter ( Table 1 ) indicates the need for an external factor modifying the nature of the environment that favors the structural transformation leading to the formation of the amyloid form.…”

Section: Discussionmentioning

confidence: 99%

In Silico Modeling of the Influence of Environment on Amyloid Folding Using FOD-M Model

Roterman

Stąpor

Fabian

et al. 2021

IJMS

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The role of the environment in amyloid formation based on the fuzzy oil drop model (FOD) is discussed here. This model assumes that the hydrophobicity distribution within a globular protein is consistent with a 3D Gaussian (3DG) distribution. Such a distribution is interpreted as the idealized effect of the presence of a polar solvent—water. A chain with a sequence of amino acids (which are bipolar molecules) determined by evolution recreates a micelle-like structure with varying accuracy. The membrane, which is a specific environment with opposite characteristics to the polar aquatic environment, directs the hydrophobic residues towards the surface. The modification of the FOD model to the FOD-M form takes into account the specificity of the cell membrane. It consists in “inverting” the 3DG distribution (complementing the Gaussian distribution), which expresses the exposure of hydrophobic residues on the surface. It turns out that the influence of the environment for any protein (soluble or membrane-anchored) is the result of a consensus factor expressing the participation of the polar environment and the “inverted” environment. The ratio between the proportion of the aqueous and the “reversed” environment turns out to be a characteristic property of a given protein, including amyloid protein in particular. The structure of amyloid proteins has been characterized in the context of prion, intrinsically disordered, and other non-complexing proteins to cover a wider spectrum of molecules with the given characteristics based on the FOD-M model.

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Solubility and Aggregation of Selected Proteins Interpreted on the Basis of Hydrophobicity Distribution

Cited by 12 publications

References 50 publications

How Honey Bee Vitellogenin Holds Lipid Cargo: A Role for the C-Terminal

How Honey Bee Vitellogenin Holds Lipid Cargo: A Role for the C-Terminal

A novel strategy for developing vaccine candidate against Jaagsiekte sheep retrovirus from the envelope and gag proteins: an in-silico approach

In Silico Modeling of the Influence of Environment on Amyloid Folding Using FOD-M Model

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