Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey - page 142

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Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session II
83-POS Board 36
Structural and Dynamics Aspects of ASC Speck Assembly
Ali C. Sahillioglu3,4, Fidan Sümbül1,2, Nesrin Ozoren3,4, Turkan Haliloglu1,2.
1Bogazici University, Istanbul, Turkey, 2Bogazici University, Istanbul, Turkey, 3Bogazici
University, Istanbul, Turkey, 4Bogazici University, Istanbul, Turkey.
The inflammasome complexes are activated by rapid formation of ASC speck which acts as an
adaptor that bridges procaspase-1 to the receptors. The resemblance between the ASC speck and
aggresome raises the question whether the ASC speck formation is a result of specific
interactions between PYD and CARD which both belong to the death fold superfamily or simply
aggregation of hydrophobic patches of ASC proteins. To address this question, we performed
structure and dynamics based analyses on the ASC protein using Gaussian Network Model
(GNM) of PYD and CARD, and Molecular Dynamics (MD) simulations of the wild type and in-
silico mutated PYD, with the mutational analysis on the ASC structure and its separated domains
in human cells, we show that the ASC speck formation is an organized structure based on
specific homophilic but not heterophilic interactions by PYD and CARD separately. PYD is able
to use alternative interaction modes other than type I that might be important in compaction of
the ASC speck. We propose a model in which filament formation is the first level of organization
in the ASC speck and filaments further compact in a higher organization level.