Several important biological processes are initiated by the binding
of a protein to a specific site on the DNA. The strategy adopted by a protein,
called transcription factor (TF), for searching its specific binding site on the
DNA has been investigated over several decades. In recent times the effects
obstacles, like DNA-binding proteins, on the search by TF has begun to receive
attention. RNA polymerase (RNAP) motors collectively move along a segment
of the DNA during a genomic process called transcription. This RNAP trac
is bound to affect the diffusive scanning of the same segment of the DNA by
a TF searching for its binding site. Motivated by this phenomenon, here we
develop a kinetic model where a ‘particle’, that represents a TF, searches
for a specific site on a one-dimensional lattice. On the same lattice another
species of particles, each representing a RNAP, hop from left to right exactly
as in a totally asymmetric simple exclusion process (TASEP) which forbids
simultaneous occupation of any site by more than one particle, irrespective of
their identities. Although the TF is allowed to attach to or detach from any
lattice site, the RNAPs can attach only to the first site at the left edge and
detach from only the last site on the right edge of the lattice. We formulate the search as a first-passage process; the time taken to reach the target site
for the first time, starting from a well defined initial state, is the search time.
By approximate analytical calculations and Monte Carlo (MC) computer
simulations, we calculate the mean search time. We show that RNAP traffic
rectifies the diffusive motion of TF to that of a Brownian ratchet, and the
mean time of successful search can be even shorter than that required in the
absence of RNAP traffic. Moreover, we show that there is an optimal rate of
detachment that corresponds to the shortest mean search time.
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Moving while you’re stuck: a macroscopic demonstration of an active system inspired by binding-mediated transport in biology
Diffusive motion is typically constrained when particles bind to the medium through which they move. However, when binding is transient and the medium is made of flexible filaments, each association or dissociation event produces a stochastic force that can overcome the medium stickiness and enable motion. This mechanism is amply used by biological systems where the act of balancing binding and displacement robustly achieves key functionalities, including bacterial locomotion or selective active filtering in cells. Here we demonstrate the feasibility of making a dynamic system with macroscopic features, in which analogous binding-mediated motion can be actively driven, precisely tuned, and conveniently studied. We find an optimal binding affinity and number of binding sites for diffusive motion, and an inverse relationship between viscosity and diffusivity.
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- Award ID(s):
- 1761918
- NSF-PAR ID:
- 10295774
- Date Published:
- Journal Name:
- Soft Matter
- Volume:
- 17
- Issue:
- 10
- ISSN:
- 1744-683X
- Page Range / eLocation ID:
- 2957 to 2962
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Superresolution, single-particle tracking reveals effects of the cationic antimicrobial peptide LL-37 on the
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- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D0SM01808B
