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Siderovski Lab Research Interests GoLoco Motif Proteins: The GoLoco motif was originally identified by our group as a novel 19 residue signature in RGS12, RGS14, and Drosophila Loco. GoLoco motifs bind G-alpha subunits in a nucleotide-dependent manner. Surprisingly, these proteins are central mediators of mitotic spindle organization and force generation required for chromosomal segregation during mitosis:  Willard, Kimple, Siderovski. (2004)  Ann. Rev. Biochem. 73: 925-51. The Return of the GDI: The GoLoco motif in cell division. Kimple et al. (2004) Biochemical Journal 378: 801-8. Guanine nucleotide dissociation inhibitor activity of the triple GoLoco motif protein G18. Colombo et al. (2003) Science 300:1957-61. Translation of polarity cues into asymmetric spindle positioning in C. elegans embryos. Kimple, Willard, Siderovski. (2002)  Mol. Interv. 2: 88-100. The GoLoco Motif: Heralding a new tango between G protein signaling and cell division. Kimple et al. (2002) Nature 416: 878-881. Structural determinants for GoLoco-induced inhibition of nucleotide release by Galpha subunits. Siderovski et al. (1999) TIBS 24:340-341. RGS12 & RGS14 GoLoco motifs are G alpha(i) interaction sites with GDI activity. "Regulator of G-protein Signaling" (RGS) Proteins: The Siderovski lab, before arriving in Chapel Hill, discovered the RGS proteins through research into immediate-early genes involved in T-cell activation: Siderovski et al. (1996) Current Biology 6:211-212. A new family of regulators of G-protein-coupled receptors. The following review on the RGS proteins in Nature Reviews Drug Discovery can be considered the "Siderovski Lab Manifesto" for the next several decades when it comes to our pursuit of these novel negative regulators of G protein-coupled receptor signaling as targets for therapeutic intervention: Neubig & Siderovski (2002) Nat. Rev. Drug Disc. 1: 187-197. Regulators of G-protein signalling as new central nervous system drug targets. The GGL domain and R7-subfamily RGS proteins The Siderovski lab first discovered the "G-gamma-like" or GGL domain within a subfamily of RGS proteins (RGS6, RGS7, RGS9, and RGS11) -- this GGL domain binds to the neurospecific Gbeta5 subunit and forms one of our structural biology targets in Project I of our NIH Program Project Grant "G-protein Signal Integration by Multifunctional Proteins": Sondek & Siderovski (2001) Biochem. Pharm. 61: 1329-1337. Ggamma-like (GGL) domains: new frontiers in G-protein signaling and beta-propeller scaffolding.