Publications by authors named "Athira George"

3 Publications

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Disordered protein interactions for an ordered cellular transition: Cdc2-like kinase 1 is transported to the nucleus via its Ser-Arg protein substrate.

J Biol Chem 2019 06 7;294(24):9631-9641. Epub 2019 May 7.

From the Department of Pharmacology, University of California San Diego, La Jolla, California 92093-0636

Serine-arginine (SR) proteins are essential splicing factors that promote numerous steps associated with mRNA processing and whose biological function is tightly regulated through multi-site phosphorylation. In the nucleus, the cdc2-like kinases (CLKs) phosphorylate SR proteins on their intrinsically disordered Arg-Ser (RS) domains, mobilizing them from storage speckles to the splicing machinery. The CLKs have disordered N termini that bind tightly to RS domains, enhancing SR protein phosphorylation. The N termini also promote nuclear localization of CLKs, but their transport mechanism is presently unknown. To explore cytoplasmic-nuclear transitions, several classical nuclear localization sequences in the N terminus of the CLK1 isoform were identified, but their mutation had no effect on subcellular localization. Rather, we found that CLK1 amplifies its presence in the nucleus by forming a stable complex with the SR protein substrate and appropriating its NLS for transport. These findings indicate that, along with their well-established roles in mRNA splicing, SR proteins use disordered protein-protein interactions to carry their kinase regulator from the cytoplasm to the nucleus.
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http://dx.doi.org/10.1074/jbc.RA119.008463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579451PMC
June 2019

Repurposing proteins for new bioinorganic functions.

Essays Biochem 2017 05 9;61(2):245-258. Epub 2017 May 9.

Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0356, U.S.A.

Inspired by the remarkable sophistication and complexity of natural metalloproteins, the field of protein design and engineering has traditionally sought to understand and recapitulate the design principles that underlie the interplay between metals and protein scaffolds. Yet, some recent efforts in the field demonstrate that it is possible to create new metalloproteins with structural, functional and physico-chemical properties that transcend evolutionary boundaries. This essay aims to highlight some of these efforts and draw attention to the ever-expanding scope of bioinorganic chemistry and its new connections to synthetic biology, biotechnology, supramolecular chemistry and materials engineering.
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http://dx.doi.org/10.1042/EBC20160068DOI Listing
May 2017

Human SAS-6 C-Terminus Nucleates and Promotes Microtubule Assembly in Vitro by Binding to Microtubules.

Biochemistry 2015 Oct 7;54(41):6413-22. Epub 2015 Oct 7.

School of Biology, Indian Institute of Science Education and Research Thiruvananthapuram , CET Campus, Thiruvananthapuram 695016, Kerala, India.

Centrioles are essential components of the animal centrosome and play crucial roles in the formation of cilia and flagella. They are cylindrical structures composed of nine triplet microtubules organized around a central cartwheel. Recent studies have identified spindle assembly abnormal protein SAS-6 as a critical component necessary for formation of the cartwheel. However, the molecular details of how the cartwheel participates in centriolar microtubule assembly have not been clearly understood. In this report, we show that the C-terminal tail (residues 470-657) of human SAS-6, HsSAS-6 C, the region that has been shown to extend toward the centriolar wall where the microtubule triplets are organized, nucleated and induced microtubule polymerization in vitro. The N-terminus (residues 1-166) of HsSAS-6, the domain known to be involved in formation of the central hub of the cartwheel, did not, however, exert any effect on microtubule polymerization. HsSAS-6 C bound to the microtubules and localized along the lengths of the microtubules in vitro. Microtubule pull-down and coimmunoprecipitation (Co-IP) experiments with S-phase synchronized HeLa cell lysates showed that the endogenous HsSAS-6 coprecipitated with the microtubules, and it mediated interaction with tubulin. Isothermal calorimetry titration and size exclusion chromatography showed that HsSAS-6 C bound to the αβ-tubulin dimer in vitro. The results demonstrate that HsSAS-6 possesses an intrinsic microtubule assembly promoting activity and further implicate that its outer exposed C-terminal tail may play critical roles in microtubule assembly and stabilizing microtubule attachment with the centriolar cartwheel.
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http://dx.doi.org/10.1021/acs.biochem.5b00978DOI Listing
October 2015
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