Kinetics and modeling of diphtheria toxin (FA) and actin interaction


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VAROL B., ünlü a., hacıosmanoğlu e., BEKTAŞ M., NURTEN R.

10th European Biophysics Congress, Dresden, Germany, 18 - 22 July 2015, pp.30

  • Publication Type: Conference Paper / Full Text
  • City: Dresden
  • Country: Germany
  • Page Numbers: pp.30
  • Istanbul University Affiliated: Yes

Abstract

Diphtheria toxin (DTx) is separated into two fragments after
limited proteolytic digestion. Fragment A (FA) (21 kDa)
has an enzymatic activity (ADP-ribosyltransferase) at the
end of the N-terminal that catalyses the transfer of an ADPribosyl
group of NAD to a post-translationally modified histidine
(diphthamide) residue on eukaryotic elongation factor
2 (eEF2). Fragment B (FB) (39 kDa) that provides the
connection between the cell and holotoxin. Actin, is the
main component of the microfilament structure in eukaryotic
cells. Moreover, it interacts with a group of proteins and
acts as a junction in the signal pathways. For this hence, it
was shown that DTx causes actin depolymerization. In this
study, it was shown by gel filtration and viscosity measurements
that FA can interact with both G (globular) and F
(filamentous) actin from the positive end. This interaction
was inhibited by gelsolin or DNase I. Additevely, FA and Gactin
were obtained with homology modelling and interacted
with (NAMD, Docking) methods. The possible interaction
site with high binding energy, was determined with the Maestro
program that was devoloped by Max-Planck Instute.