Proceedings of the National Academy of Sciences | VOL. 119
Read

Threading single proteins through pores to compare their energy landscapes

Publication Date Sep 19, 2022

Abstract

Translocation of proteins is correlated with structural fluctuations that access conformational states higher in free energy than the folded state. We use electric fields at the solid-state nanopore to control the relative free energy and occupancy of different protein conformational states at the single-molecule level. The change in occupancy of different protein conformations as a function of electric field gives rise to shifts in the measured distributions of ionic current blockades and residence times. We probe the statistics of the ionic current blockades and residence times for three mutants of the λ -repressor family in order to determine the number of accessible conformational states of each mutant and evaluate the ruggedness of their free energy landscapes. Translocation becomes faster at higher electric fields when additional flexible conformations are available for threading through the pore. At the same time, folding rates are not correlated with ease of translocation; a slow-folding mutant with a low-lying intermediate state translocates faster than a faster-folding two-state mutant. Such behavior allows us to distinguish among protein mutants by selecting for the degree of current blockade and residence time at the pore. Based on these findings, we present a simple free energy model that explains the complementary relationship between folding equilibrium constants and translocation rates.

Concepts

Folding Equilibrium Constants Current Residence Protein Conformational States Free Energy Free Energy Landscapes Change In Occupancy Residence Times Translocation Of Proteins Folding Rates Current Blockades

Round-ups are the summaries of handpicked papers around trending topics published every week. These would enable you to scan through a collection of papers and decide if the paper is relevant to you before actually investing time into reading it.

Coronavirus Research Articles published between Nov 28, 2022 to Dec 04, 2022

R DiscoveryDec 05, 2022
R DiscoveryArticles Included:  5

The coronavirus disease 2019 (COVID-19) is a contagious disease that is caused by a novel coronavirus. Bentham is offering subject-based scholarly con...

Read More

Climate change Research Articles published between Nov 28, 2022 to Dec 04, 2022

R DiscoveryDec 05, 2022
R DiscoveryArticles Included:  5

We use cookies to improve your website experience. To learn about our use of cookies and how you can manage your cookie settings, please see our Cooki...

Read More

Quality Of Education Research Articles published between Nov 28, 2022 to Dec 04, 2022

R DiscoveryDec 05, 2022
R DiscoveryArticles Included:  4

Introduction: The Internet is an extensively used source of medical education by the public. YouTube is a valuable source of information which can be ...

Read More

Gender Equality Research Articles published between Nov 28, 2022 to Dec 04, 2022

R DiscoveryDec 05, 2022
R DiscoveryArticles Included:  3

Gender equity in the classroom is important for teachers to think about in order to ensure they are creating safe environments that allow their studen...

Read More

Coronavirus Pandemic

You can also read COVID related content on R COVID-19

R ProductsCOVID-19

ONE PROBLEM . ONE PURPOSE . ONE PLACE

Creating the world’s largest AI-driven & human-curated collection of research, news, expert recommendations and educational resources on COVID-19

COVID-19 Dashboard

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on “as is” basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The Copyright Law.