Albany 2015:Book of Abstracts

Albany 2015
Conversation 19
June 9-13 2015
©Adenine Press (2012)

Electrostatics of E. coli CRP Transcription Factor Match That of Its Binding Sites

Transcription regulation is well known to be influenced by physical properties of genome DNA, especially by its electrostatic interactions with different regulative proteins, in particular the primary recognition and regulation of transcription by RNA-polymerase. This enzyme may identify promoters and evaluate their strength due to the peculiarity of their electrostatic profiles. The same problem of recognition of a limited number of specific sequences in the long DNA molecule faces also transcription factors. To reveal the role of electrostatic properties here we studied that of binding sites of a typical transcription factor -CRP - together with its its own dimer molecule.

Electrostatics distribution on CRP dimer surface reflects the DNA electrostatics of its binding sites. The averaged profiles of the DNA electrostatic potential aligned around the binding sites centers exhibit the pronounced rise in the negative potential value with the characteristic profile in the consensus area (being a palindrome). The extensive (around 100-300 bp long), symmetrical overall potential rise can not be explained by the influence of the consensus alone and reflects the sequence organization of the flanking regions, contributing to the high potential area formation. Apparently this sequence organization was selected evolutionary to support the binding site recognition by the regulation protein molecule and its retention. CRP dimer have strong electropositive patch at the DNA binding area, that is surrounded by mostly electronegative or neutral surface. This may lead to proper orientation of the molecule and facilitate DNA sites recognition and binding.

The high potential area is relatively AT-enriched, which is reflected in that different other physical properties, especially energy-related, exhibit similar behavior, though their size and parameters are different. This may facilitate binding and accompanying DNA bending. However, these are for CRP (or other transcription factors) purposes only as they lie away from the sensitive promoter regions.


Fig 1: Distribution of electrostatic potential around 1000 b.p. of CRP binding sites (averaged). Vertical axe: electrostatic potential in ēÅ. Horizontal axe: sequence length in Å aligned around CRP binding sites (green vertical band) centers. Inset: 100 b.p. fragment with CRP ribbon model shown at the same scale.


Fig 2: Electrostatic potential surface of CRP molecule dimer on the DNA-binding side (top), lateral and bottom sides. First row: protein alone, second: with DNA superimposed, third: ribbon models with DNA. Blue corresponds to negative electrostatic potential, red - to positive, white - neutral.

DEPPDB (deppdb.psn.ru) and its tools were used to make the analysis. This research has been supported by RFBR grant 14-44-03683.

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Eugenia A. Krutinina
Gleb G. Krutinin
Svetlana G. Kamzolova
Alexander A. Osypov*

Institute of Cell Biophysics of RAS
Pushchino Moscow Region, Russia, 142290

Ph: +7(929) 606-9828