title: Structural and dynamics aspects of ASC speck assembly.
abstract: Activation of the inflammasome is accompanied by rapid formation of a micrometer-sized perinuclear structure called the ASC speck, a platform for caspase-1 activity. The ASC speck is often referred to as an aggregate and shares certain features with aggresomes. It is thus an open question whether the ASC speck formation takes place via nonspecific aggregation of hydrophobic patches or specific interactions of its domains; PYD and CARD, which belong to the death fold superfamily. Bringing together structure and dynamics studies using the Gaussian network model of PYD and CARD, and molecular dynamics simulations of the wild-type and in silico mutated PYD, with the mutational analysis on the ASC structure and its separate domains in human cells, we show that the ASC speck is an organized structure with at least two levels of distinct compaction mechanisms based on the specific interactions of PYD and CARD.
authors.affiliation: Department of Molecular Biology and Genetics, Apoptosis and Cancer Immunology Laboratory (AKIL), Bogazici University, 34470 Istanbul, Turkey.
authors.forename: Ali Can
authors.initials: AC
authors.lastname: Sahillioglu
authors.affiliation: Department of Chemical Engineering and Polymer Research Center, Bogazici University, 34470 Istanbul, Turkey.
authors.forename: Fidan
authors.initials: F
authors.lastname: Sumbul
authors.affiliation: Department of Molecular Biology and Genetics, Apoptosis and Cancer Immunology Laboratory (AKIL), Bogazici University, 34470 Istanbul, Turkey; Center for Life Sciences and Technologies, Bogazici University, 34470 Istanbul, Turkey. Electronic address: nesrin.ozoren@boun.edu.tr.
authors.forename: Nesrin
authors.initials: N
authors.lastname: Ozoren
authors.affiliation: Department of Chemical Engineering and Polymer Research Center, Bogazici University, 34470 Istanbul, Turkey; Center for Life Sciences and Technologies, Bogazici University, 34470 Istanbul, Turkey. Electronic address: haliloglut@boun.edu.tr.
authors.forename: Turkan
authors.initials: T
authors.lastname: Haliloglu
mesh_terms: D053468:CARD Signaling Adaptor Proteins; D020170:Caspase 1 / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D055503:Protein Multimerization
chemical_list: D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D058847:Inflammasomes; C402202:PYCARD protein, human; D020170:Caspase 1