Piraveen Piv Gopalasingam | European Molecular Biology Laboratory (original) (raw)
PhD in structural biology using protein NMR, SAXS and other biophysical/biochemical techniques to study protein-ligand interactions within human signalling cascades. Experience with membrane proteins, bacterial azoreductases and molecular docking + structural bioinformatics
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Books by Piraveen Piv Gopalasingam
Src homology 2 (SH2) domains are signalling modules consisting of 100 amino acid residues which t... more Src homology 2 (SH2) domains are signalling modules consisting of 100 amino acid residues which typically recognize phosphotyrosine-containing protein sequences. As such, they mediate protein–protein interactions in order to assemble signalling complexes and transduce information to alter cellular behaviour and physiology. Here we review the progress in understanding the molecular functions and structures of SH2 domains since their discovery in 1986. Diverse binding modes are revealed by studies of a variety of ligand complexes, suggesting that their mechanisms have adapted throughout the evolution in tandem with tyrosine kinases and phosphatases. Together they form the information networks responsible for development of the cellular phosphoproteome and the ensuing multicellular complexity found in higher eukaryotes. Understanding the structures, dynamics and interactions of these remarkable domains at a more predictive level is providing a rational basis for designing targeted interventions into the many disorders that result from deregulated phosphotyrosine signalling.
Papers by Piraveen Piv Gopalasingam
Recently, major progress has been made in uncovering the mechanisms of how insulin engages its re... more Recently, major progress has been made in uncovering the mechanisms of how insulin engages its receptor and modulates downstream signal transduction. Here, we present in detail the current structural knowledge surrounding the individual components of the complex, binding sites, and dynamics during the activation process. A novel kinase triggering mechanism, the ‘bow-arrow model’, is proposed based on current knowledge and computational simulations of this system, in which insulin, after its initial interaction with binding site 1, engages with site 2 between the fibronectin type III (FnIII)-1 and -2 domains, which changes the conformation of FnIII-3 and eventually translates into structural changes across the membrane. This model provides a new perspective on the process of insulin binding to its receptor and, thus, could lead to future novel drug discovery efforts.
Src homology 2 (SH2) domains are signalling modules consisting of 100 amino acid residues which t... more Src homology 2 (SH2) domains are signalling modules consisting of 100 amino acid residues which typically recognize phosphotyrosine-containing protein sequences. As such, they mediate protein–protein interactions in order to assemble signalling complexes and transduce information to alter cellular behaviour and physiology. Here we review the progress in understanding the molecular functions and structures of SH2 domains since their discovery in 1986. Diverse binding modes are revealed by studies of a variety of ligand complexes, suggesting that their mechanisms have adapted throughout the evolution in tandem with tyrosine kinases and phosphatases. Together they form the information networks responsible for development of the cellular phosphoproteome and the ensuing multicellular complexity found in higher eukaryotes. Understanding the structures, dynamics and interactions of these remarkable domains at a more predictive level is providing a rational basis for designing targeted interventions into the many disorders that result from deregulated phosphotyrosine signalling.
Recently, major progress has been made in uncovering the mechanisms of how insulin engages its re... more Recently, major progress has been made in uncovering the mechanisms of how insulin engages its receptor and modulates downstream signal transduction. Here, we present in detail the current structural knowledge surrounding the individual components of the complex, binding sites, and dynamics during the activation process. A novel kinase triggering mechanism, the ‘bow-arrow model’, is proposed based on current knowledge and computational simulations of this system, in which insulin, after its initial interaction with binding site 1, engages with site 2 between the fibronectin type III (FnIII)-1 and -2 domains, which changes the conformation of FnIII-3 and eventually translates into structural changes across the membrane. This model provides a new perspective on the process of insulin binding to its receptor and, thus, could lead to future novel drug discovery efforts.