Browsing by Subject "Actin"
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Item Elastic network & finite element model to study actin protein mechanics & its molecular elasticity(2010-12) Marquez, Joel David; Moon, T. J. (Tess J.); Ren, PengyuWhile there have been many recently developed Elastic Network Models (ENM) to calculate the fluctuation dynamics of proteins, e.g., Gaussian Network Model (GNM), Anisotropic Network Model (ANM), Distance Network Model (DNM), the concept of loading these models to study the molecular mechanics and constitutive behavior of structural proteins has remained relatively untouched, until very recently. This work entails using the ANM as the framework for developing a finite element model of a 9–monomer strand of actin. Critical input parameters to the model, such as the cutoff radius, r[subscript c], and spring constant, k, are generated by matching the all-atom steered molecular dynamics (SMD) residue displacements to that of the ANM. The parameters yielding the best match between the SMD and structural ENM (SENM) simulations will then be input into the finite element model (FEM) for a more in depth analysis. The finite element model incorporates a 9–monomer strand of actin. The F–actin strand is subjected axial and torsional loads comparable to those seen in vivo. Key areas of interest in the protein are examined, such as the nucleotide binding pocket (NBP) and the DNase I binding loop, to demonstrate how loading affects the protein’s conformation. Local residue displacements are tracked in an effort to garner a better understanding of how various loads are transmitted through F–actin during key events. Insights and conclusions are discussed along with the implications of this work.Item Myosin II alters the viscoelasticity and self-assembly properties of actin networks(2002-05) Humphrey, David Harold; Käs, Joseph A.; Molineux, IanItem Systematic analysis of Rfx2 target genes in vertebrate multiciliated cells(2017-08-25) Tu, Fan; Wallingford, John B.; Marcotte, Edward M.; Miller, Kyle M.; O'Halloran, Theresa; Paull, Tanya T.Multiciliated cells (MCCs) drive directional fluid flow in diverse tubular organs and are essential for development and homeostasis of the vertebrate central nervous system, airway, and reproductive tracts. These cells are characterized by dozens or hundreds of long, motile cilia that beat in a coordinated and polarized manner. In recent years, genomic studies have not only elucidated the transcriptional hierarchy for MCC specification, but also identified myriad new proteins that govern MCC ciliogenesis, cilia beating, or cilia polarization. Interestingly, this burst of genomic data has also highlighted the obvious importance of the “ignorome,” that large fraction of vertebrate genes that remain only poorly characterized. Understanding the function of novel proteins with little prior history of study presents a special challenge, especially when faced with large numbers of such proteins. Here, we explored the MCC ignorome by defining the subcellular localization of 260 poorly defined proteins in vertebrate MCCs in vivo. Based on this localization data, we selected some targets of MCC ignorome for further functional studies because they could possibly play key roles in the regulation of ciliogenesis. We characterized Myo5c as the motor for basal body apical migration, vi Arhgef18 as the RhoA signaling activator at the basal bodies, and Dennd2b as a regulator of actin network formation and ciliogenesis. All of these findings have deepened our understanding about molecular mechanisms of related cellular process. This study exemplifies the power of high content protein localization screening as the bridging step between large-scale omics data and functional study of specific proteins.