Structural means of assessing the association of hamartin and tuberin

Show simple item record Natarajan, Nalini Thiruvenkatam, Vijay 2018-01-08T12:33:52Z 2018-01-08T12:33:52Z 2017-08
dc.identifier.citation Natarajan, Nalini and Thiruvenkatam, Vijay, "Structural means of assessing the association of hamartin and tuberin", Acta Crystallographica Section A, DOI: 10.1107/S2053273317085813, vol. 73, no. a2, pp. C993, Aug. 2017. (Abstract) en_US
dc.identifier.issn 2053-2733
dc.description.abstract mTOR pathway is one of the most important and well-studied signalling cascades with respect to cancer. The majorcontrollers of mTOR are the tumour suppressors Hamartin (TSC1) and Tuberin (TSC2), which lies in the heart of this cellularsignalling pathway. Mutation in any of these genes will render them unsuccessful to possess tuberin's GTPase activitytowards Rheb, a small G-protein, which eventually keeps the mTOR activated. Such mutations lead to tuberous sclerosiscomplex, a multi-organ disease characterized by non-cancerous tumours in brain, skin, liver, kidney, lungs and heart. Also, itputs an individual at a higher risk of developing cancer in these organs.Several inhibitors are designed and still being designed for mTOR, while the actual source of the problem (TSC1 & TSC2) isleft unchecked. The main reason for this is the lack of structure for both TSC1 and TSC2. Owing to its large size, Hamartin(1164 aa) and Tuberin (1804 aa) cannot be expressed under a bacterial expression system. Hence the major focus of ourstudy is in the interaction regions of these two proteins. Since it is a small portion of these proteins, its expression isfeasible in E.coli. Hamartin's interaction region of tuberin is predicted to possess a potential leucine zipper region (81-121aa) and a putative coiled-coil domain (346-371 aa). Recent studies have structurally proven the presence of a newcomponent to the Tuberous sclerosis protein complex, which is known as TBC1D7. Many studies have been made with Tscmutated cohorts and the researchers have tried to analyze the etiology of the disease biochemically. Yet, deciphering thestructure of this tumor suppressor complex would not only satiate the search for answers in mTOR pathway but also throwlimelight on the plethora of protein-protein interactions in various other significant pathways. Knowing the structure wouldenable us to envisage the design of agonist for these proteins to enhance their tumour suppressor activity.
dc.description.statementofresponsibility by Nalini Natarajan and Vijay Thiruvenkatam
dc.format.extent vol. 73, no. a2, pp. C993
dc.language.iso en en_US
dc.publisher International Union of Crystallography en_US
dc.subject Hamartin en_US
dc.subject Tuberin en_US
dc.subject Protein-protein interactions en_US
dc.title Structural means of assessing the association of hamartin and tuberin en_US
dc.type Article en_US
dc.relation.journal Acta Crystallographica Section A

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