@article {49123,
	title = {Architecture of the human GATOR1 and GATOR1-Rag GTPases complexes.},
	journal = {Nature},
	volume = {556},
	year = {2018},
	month = {2018 Mar 28},
	pages = {64-9},
	abstract = {<p>Nutrients, such as amino acids and glucose, signal through the Rag GTPases to activate mTORC1. The GATOR1 protein complex-comprising DEPDC5, NPRL2 and NPRL3-regulates the Rag GTPases as a GTPase-activating protein (GAP) for RAGA; loss of GATOR1 desensitizes mTORC1 signalling to nutrient starvation. GATOR1 components have no sequence homology to other proteins, so the function of GATOR1 at the molecular level is currently unknown. Here we used cryo-electron microscopy to solve structures of GATOR1 and GATOR1-Rag GTPases complexes. GATOR1 adopts an extended architecture with a cavity in the middle; NPRL2 links DEPDC5 and NPRL3, and DEPDC5 contacts the Rag GTPase heterodimer. Biochemical analyses reveal that our GATOR1-Rag GTPases structure is inhibitory, and that at least two binding modes must exist between the Rag GTPases and GATOR1. Direct interaction of DEPDC5 with RAGA inhibits GATOR1-mediated stimulation of GTP hydrolysis by RAGA, whereas weaker interactions between the NPRL2-NPRL3 heterodimer and RAGA execute GAP activity. These data reveal the structure of a component of the nutrient-sensing mTORC1 pathway and a non-canonical interaction between a GAP and its substrate GTPase.</p>
},
	issn = {1476-4687},
	doi = {10.1038/nature26158},
	author = {Shen, Kuang and Huang, Rick K and Brignole, Edward J and Condon, Kendall J and Valenstein, Max L and Chantranupong, Lynne and Bomaliyamu, Aimaiti and Choe, Abigail and Hong, Chuan and Yu, Zhiheng and Sabatini, David M}
}
@article {45184,
	title = {Molecular basis for age-dependent microtubule acetylation by tubulin acetyltransferase.},
	journal = {Cell},
	volume = {157},
	year = {2014},
	month = {2014 Jun 5},
	pages = {1405-15},
	abstract = {<p>Acetylation of α-tubulin Lys40 by tubulin acetyltransferase (TAT) is the only known posttranslational modification in the microtubule lumen. It marks stable microtubules and is required for polarity establishment and directional migration. Here, we elucidate the mechanistic underpinnings for TAT activity and its preference for microtubules with slow turnover. 1.35\&nbsp;{\r A} TAT cocrystal structures with bisubstrate analogs constrain TAT action to the microtubule lumen and reveal Lys40 engaged in a suboptimal active site. Assays with diverse tubulin polymers show that TAT is stimulated by microtubule interprotofilament contacts. Unexpectedly, despite the confined intraluminal location of Lys40, TAT efficiently scans the microtubule bidirectionally and acetylates stochastically without preference for ends. First-principles modeling and single-molecule measurements demonstrate that TAT catalytic activity, not constrained luminal diffusion, is rate limiting for acetylation. Thus, because of its preference for microtubules over free tubulin and its modest catalytic rate, TAT can function as a slow clock for microtubule lifetimes.</p>
},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2014.03.061},
	author = {Szyk, Agnieszka and Deaconescu, Alexandra M and Spector, Jeffrey and Goodman, Benjamin and Valenstein, Max L and Ziolkowska, Natasza E and Kormendi, Vasilisa and Grigorieff, Nikolaus and Roll-Mecak, Antonina}
}
