Tunable Electromechanical Nanopore Trap Reveals Populations of Peripheral Membrane Protein Binding Conformations

Published

January 26, 2021

Author(s)

David Hoogerheide, Tatiana K. Rostovtseva, Daniel Jacobs, Philip A. Gurnev, Sergey M. Bezrukov

Abstract

We demonstrate that a naturally occurring nanopore of the mitochondrion, the voltage-dependent anion channel (VDAC), can be used to electromechanically trap and interrogate proteins bound to a lipid surface at the single-molecule level. Electromechanically probing α-synuclein (αSyn), an intrinsically disordered neuronal protein intimately associated with Parkinson's pathology, reveals wide variation in the time required for individual proteins to unbind from the same membrane surface. The observed distributions of unbinding times span up to three orders of magnitude and depend strongly on the lipid composition of the membrane; surprisingly, lipid membranes to which αSyn binds weakly are most likely to contain sub-populations in which unbinding is very slow. We conclude that unbinding of αSyn from the membrane surface depends not only on membrane binding affinity, but also on the conformation adopted by an individual αSyn molecule on the membrane surface.

Citation

ACS Nano

Volume

15

Issue

1

Pub Type

Journals

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Keywords

Voltage dependent anion channel, alpha-synuclein, intrinsically disordered proteins, protein-lipid interaction, single-molecule measurement, peripheral membrane proteins, energy landscape

Citation

Hoogerheide, D. , , T. , Jacobs, D. , , P. and , S. (2021), Tunable Electromechanical Nanopore Trap Reveals Populations of Peripheral Membrane Protein Binding Conformations, ACS Nano, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=931177 (Accessed April 19, 2024)