Nanoscopic surfactant behavior of the porin MspA in aqueous media

Perera, Ayomi S.; Wang, Hongwang; Shrestha, Tej B.; Troyer, Deryl L.; Bossmann, Stefan H.

doi:10.3762/bjnano.4.30

Cited by 7 publications

(5 citation statements)

References 30 publications

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“…x = 0 is the position of MspA’s constriction along the ssDNA when the NeutrAvidin is pulled against the entrance to the pore’s vestibule, and x = L domain is the position of MspA’s constriction along the ssDNA when the end of the ssDNA tail escapes from the constriction altogether. By considering the length of DNA(19) and the total size of the MspA pore(6, 20), L domain is set to be the length of 14 nucleotides, with length per base a 0 =0.5nm. According to the first-passage approach, we define the probability of passage times as f esc ( x 0 , t ) dt , which represents the probability that the DNA escapes from the pore back into solution within a time between t and t + dt, given an initial starting position x 0 .…”

Section: Resultsmentioning

confidence: 99%

Thermal motion of DNA in an MspA pore

Fleming

Szalay

et al. 2015

Preprint

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We report on an experiment and calculations that determine the thermal motion of a voltageclamped ssDNA-NeutrAvidin complex in an MspA nanopore. The electric force and diffusion constant of DNA inside an MspA pore have been determined in order to evaluate DNA's thermal position fluctuations. We show that an out-of-equilibrium state returns to equilibrium so quickly that experiments usually measure a weighted average over the equilibrium position distribution. Averaging over the equilibrium position distribution is consistent with results of state-of-the-art nanopore sequencing experiments. It is shown that a reduction in thermal averaging can be achieved by increasing the electrophoretic force used in nanopore sequencing devices.

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Section: Resultsmentioning

confidence: 99%

Thermal motion of DNA in an MspA pore

Fleming

Szalay

et al. 2015

Preprint

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“…Remarkably, close inspection of the Mtb cell surface reveals the formation of MAD1 cylindrical assemblies that are ~14 nm in diameter (Figure 4d, magnified image and inset), which approximates the size of the MspA porin head (9 nm in width). 31 TEM images shown in Fig. 4e demonstrate that at low MAD1 concentrations (0.1 x MIC) cytoplasmic granules begin to develop, which are indicative of an early cellular stress response.…”

Section: Mtb-instructed Mad1 Assembly Into Supramolecular Nano-lyticsmentioning

confidence: 90%

Pathogen-Specific De Novo Antimicrobials Engineered Through Membrane Porin Biomimicry

Simonson¹,

Mongia²,

Aronson³

et al. 2020

Preprint

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Precision antimicrobials that can kill pathogens without damaging host commensals hold potential to cure disease without antibiotic-associated dysbiosis. Here we report the de novo design of host defense peptides that have been rationally engineered to precisely target specific pathogens by mimicking key molecular features of the target microbe’s unique channel-forming membrane proteins, or porins. This biomimetic strategy exploits physical and structural motifs of the pathogen envelope, rather than targeting resistance-susceptible protein biochemical pathways, to construct fast-acting precision bacteriolytics. Utilizing this approach, we design an antitubercular sequence that undergoes instructed, tryptophan-zippered assembly within the mycolic-acid rich outer membrane of Mycobacterium tuberculosis (Mtb) to specifically kill the pathogen without collateral toxicity towards lung commensals or host tissue. These mycomembrane-templated mechanisms are rapid and synergistically enhance the potency of antibiotics that otherwise poorly diffuse across the rigid Mtb envelope, particularly those that exploit porins for antimycobacterial activity. This new porin-mimetic paradigm may serve as a conceptual basis for the directed design of new narrow-spectrum antimicrobial scaffolds.

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“…The zeta potential  of MspA vesicles has been reported and discussed in an earlier report. 20 In 1X PBS, the  value of MspA is slightly positive ( = 10 ± 14 mV)in the low temperature range (296 to 320 K). Above 320 K, a remarkable increase of  to 100 ± 12 mV at 344 K is observed.…”

Section: Temperaturementioning

confidence: 93%

“…We also investigated the aggregation of individual MspA 20 and RuC2/MspA mixtures in dilute 1x PBS aqueous solutions as a function of temperature by using dynamic light scattering. 21 In a previous report, we showed that MspA has a distinct tendency to aggregate with increasing temperature, 20 and the maximum diameter of the MspA vesicles was ~180 nm at 312 K. We established that MspA aggregation proceeds due to hydrophobic interactions between the docking zones of the proteins (see Figure 1a). Although hydrophobic interaction is the major mechanism behind the aggregation behavior of MspA, we also found evidence of contributions from hydrogen bonding and/or ionic interactions to the supramolecular behavior of MspA.…”

Section: Aggregation Of Mspa and Ruc2 By Dynamic Light Scatteringmentioning

confidence: 99%

Channel Blocking of MspA Revisited

Perera

Wang²,

Basel³

et al. 2012

Langmuir

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Porin A from Mycobacterium smegmatis (MspA) is a highly stable, octameric channel protein, which acts as the main transporter of electrolytes across the cell membrane. MspA features a narrow, negatively charged constriction zone, allowing stable binding of various analytes thereby blocking the channel. Investigation of channel blocking of mycobacterial porins is of significance in developing alternate treatment methods for tuberculosis. The concept that ruthenium(II)quaterpyridinium complexes have the capability to act as efficient channel blockers for MspA and related porins, emerged after very high binding constants were measured by high-performance liquid chromatography and steady-state luminescence studies. Consequently, the interactions between the ruthenium(II) complex RuC2 molecules and MspA, leading to RuC2@MspA assemblies, have been studied utilizing time-resolved absorption/emission, atomic force microscopy, dynamic light scattering, ζ potential measurements, and isothermal titration calorimetry. The results obtained provide evidence for the formation of clusters/large aggregates of RuC2 and MspA. The results are of interest with respect to utilizing prospective channel blockers in porins. The combination of results from conceptually different techniques shed some light onto the chemical nature of MspA-channel blocker interactions thus contributing to the development of a paradigm for channel blocking.

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Nanoscopic surfactant behavior of the porin MspA in aqueous media

Cited by 7 publications

References 30 publications

Thermal motion of DNA in an MspA pore

Thermal motion of DNA in an MspA pore

Pathogen-Specific De Novo Antimicrobials Engineered Through Membrane Porin Biomimicry

Channel Blocking of MspA Revisited

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