Conformational Change of Transcription Factors from Search to Specific Binding: A lac Repressor Case Study
type: Dataset
description: DNA-binding proteins (DBPs) regulate and repair genes. It is therefore important to understand their dynamics. DBPs find their target sites by combining three-dimensional diffusion and one-dimensional scanning of the DNA. Here, we study the one-dimensional diffusion and DNA binding of the dimeric lac repressor (LacI) using coarse-grained molecular dynamic simulations and compare the results to experimental data. This study supports that linear diffusion along DNA combines tight rotation-coupled groove tracking and rotation-decoupled hopping, where the protein briefly dissociates and re-associates just a few base-pairs away. Tight groove tracking is crucial for target-site recognition, while hopping speeds up the overall search process. We show how the flexibility of LacI’s hinge regions ensures agility on DNA as well as faithful groove tracking. Based on our additional study of different encounter complexes, we argue that the conformational change in LacI and DNA occur simultaneously. The content of the database can be split into Starting structures, original trajectories, processed data, data for visualization, movies in 3D space (to be used in e.g. pymol) and code. The Starting structures contain .pdb files with all-atom models and .dat files with coarse-grained models. The trajectories can be found in the folders starting with diffusion_ for monomer, dimer and full-length LacI. Additionally there are trajectories of the different encounter complexes with straight and bent DNA and the two protein conformations. The processed data contains the position of the center of mass of the proteins recognition region relative to the DNA. The data is split into the different systems we studied: the full-length proteins, dimers and monomers of the search and recognition conformations as well as encounter complexes with A- and B-forms DNA. All these systems have been studied at different salt concentrations. The code CG-analysis-rackham contains the code that was used for plot…
creative work status: completed
  type: DefinedTerm
  in defined term set: http://publications.europa.eu/resource/authority/dataset-status
  term code: COMPLETED
creator: Malin Lüking
creator: Yaakov Levy
creator: Johan Elf
  type: Person
  family name: Elf
  given name: Johan
date modified: 2023-06-01
date published: 2023-01-24
funding: SNIC 2.0: Swedish National Infrastructure for Computing
  type: Grant
  funder: Swedish Research Council
funding: The physics of genetic information processing
  type: Grant
  funder: Swedish Research Council
funding: A genome wide approach to replication initiation
  type: Grant
  funder: Swedish Research Council
keywords: Medical and Health Sciences
  type: DefinedTerm
  term code: 3
keywords: Structural Biology
  type: DefinedTerm
  term code: 10601
keywords: Structural biology (incl. macromolecular modelling)
license: https://creativecommons.org/licenses/by/4.0/
publisher: Uppsala University
version: 0

PropertyValue
property ID: DOI
value: 10.17044/SCILIFELAB.21590394

Malin Lüking
type: Person
affiliation: Science for Life Laboratory
family name: Lüking
given name: Malin

Science for Life Laboratory
type: Organization

Yaakov Levy
type: Person
family name: Levy
given name: Yaakov

Swedish Research Council
type: Organization

Uppsala University
type: Organization