Biological Nanopores: Engineering on Demand

Crnković, Ana; Srnko, Marija; Anderluh, Gregor

doi:10.3390/life11010027

Cited by 42 publications

(42 citation statements)

References 223 publications

(333 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some practical and other relevant issues are noted next. 1) Improved binding between S and the pore channel can be achieved by artificially introducing residues into PFN through selective mutagenesis at a desired set of positions [40].…”

Section: Discussionmentioning

confidence: 99%

Using wide biological pores to cap and contain the COVID-19 spike protein

Sampath¹

2021

Preprint

View full text Add to dashboard Cite

Geometric analysis shows that the spike (S) protein in the COVID-19 virus (SARS-Cov-2) can fully or partially enter into the channel of a wide biological pore like perforin (PFN) or streptolysin (SLO) when the latter is anchored in a bilayer lipid membrane. The PFN channel is a β barrel formed from multiple monomers, for example a ~14 nm diameter channel is formed from 22 monomers. Coincidentally the wide canopy of S (which has three identical chains) has an enclosing diameter of ~14 nm. While inside the channel peripheral residues in the canopy may bind with residues on the pore side of the barrel. If there are no adverse cross-reactions this would effectively prevent S from interacting with a target cell. Calculations with data obtained from PDB and other sources show that there are ~12 peripheral residue triples in S within a circle of diameter ~14 nm that can potentially bind with 22 exposed residues in each barrel monomer. The revised Miyazawa-Jernighan matrix is used to calculate the binding energy of canopy-PFN barrel residue pairs. The results show a large number of binding pairs over distances of up to 38 Å into the pore. This geometric view of capture and containment points to the possibility of using biological pores to neutralize SARS-Cov-2 in its many variant forms. Some necessary conditions that must be satisfied for such neutralization to occur are noted. A wide pore (such as PFN or SLO) can also be used in an electrolytic cell to detect the presence of SARS-Cov-2, which would cause a large-sized blockade of the base current (the ionic current in a fully open pore). It can further be used to quantify the virus level in the sample. Solid-state pores, which have several advantages over biological ones, can be used instead; immune rejection is not an issue and there is no need for the spike or the virus to bind to the pore.

show abstract

Section: Discussionmentioning

confidence: 99%

Using wide biological pores to cap and contain the COVID-19 spike protein

Sampath¹

2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Some practical issues are noted next. 1) Improved binding between S and the pore channel can be achieved by artificially introducing residues into PFN through selective mutagenesis at a desired set of positions [35].…”

Section: Discussionmentioning

confidence: 99%

Using wide biological pores to cap and contain the COVID-19 spike protein

Sampath¹

2021

Preprint

View full text Add to dashboard Cite

Geometric analysis shows that the spike (S) protein in the COVID-19 virus (SARS-Cov-2) can fully or partially enter into the channel of a wide biological pore like perforin (PFN) or streptolysin (SLO) when the latter is anchored in a bilayer lipid membrane. The PFN channel is a β barrel formed from multiple monomers, for example a ~14 nm diameter channel is formed from 22 monomers. Coincidentally the wide canopy of S (which has three identical chains) has an enclosing diameter of ~14 nm. While inside the channel peripheral residues in the canopy may bind with residues on the pore side of the barrel. If there are no adverse cross-reactions this would effectively prevent S from interacting with a target cell. Calculations with data obtained from PDB and other sources show that there are ~12 peripheral residue triples in S within a circle of diameter ~14 nm that can potentially bind with 22 exposed residues in each barrel monomer. The revised Miyazawa-Jernighan matrix is used to calculate the binding energy of canopy-PFN barrel residue pairs. The results show a large number of binding pairs over distances of up to 38 Å into the pore. This geometric view of capture and containment points to the possibility of using biological pores to neutralize SARS-Cov-2 in its many variant forms. Some necessary conditions that must be satisfied for such neutralization to occur are noted. A wide pore (such as PFN or SLO) can also be used in an electrolytic cell to detect the presence of SARS-Cov-2, which, by blocking the pore would cause a near total blockade of the base current (the ionic current in a fully open pore).

show abstract

“…Single-channel conductance (SCC) is another powerful and ubiquitous technique used to study individual nanopores [113][114][115][116][117][118] (Figure 3b). By establishing an electric potential across an impermeable bilayer, the presence of a membrane disruption (due to an arc or pore) can be detected by current flow.…”

Section: Single-channel Conductancementioning

confidence: 99%

“…This includes the size distribution of the nanopore, interactions with or binding partners (e.g. Vip1/2), as well as pore assembly pathways and kinetics in the context of systems that form pores via a growing-arc mechanism (Figure 1b) [113][114][115][116][117]. Indeed, SCC forms the technological foundation of new polymer sequencing methods (see applications below).…”

Section: Single-channel Conductancementioning

confidence: 99%

Challenges and approaches to studying pore-forming proteins

Benton

Bayly-Jones

2021

Biochemical Society Transactions

View full text Add to dashboard Cite

Pore-forming proteins (PFPs) are a broad class of molecules that comprise various families, structural folds, and assembly pathways. In nature, PFPs are most often deployed by their host organisms to defend against other organisms. In humans, this is apparent in the immune system, where several immune effectors possess pore-forming activity. Furthermore, applications of PFPs are found in next-generation low-cost DNA sequencing, agricultural crop protection, pest control, and biosensing. The advent of cryoEM has propelled the field forward. Nevertheless, significant challenges and knowledge-gaps remain. Overcoming these challenges is particularly important for the development of custom, purpose-engineered PFPs with novel or desired properties. Emerging single-molecule techniques and methods are helping to address these unanswered questions. Here we review the current challenges, problems, and approaches to studying PFPs.

show abstract

Biological Nanopores: Engineering on Demand

Cited by 42 publications

References 223 publications

Using wide biological pores to cap and contain the COVID-19 spike protein

Using wide biological pores to cap and contain the COVID-19 spike protein

Using wide biological pores to cap and contain the COVID-19 spike protein

Challenges and approaches to studying pore-forming proteins

Contact Info

Product

Resources

About