دورية أكاديمية
Structure of the Schizosaccharomyces pombe Gtr-Lam complex reveals evolutionary divergence of mTORC1-dependent amino acid sensing.
العنوان: | Structure of the Schizosaccharomyces pombe Gtr-Lam complex reveals evolutionary divergence of mTORC1-dependent amino acid sensing. |
---|---|
المؤلفون: | Tettoni SD; Program in Molecular Medicine, University of Massachusetts Chan Medical School, 373 Plantation Street, Worcester, MA 01605, USA., Egri SB; Program in Molecular Medicine, University of Massachusetts Chan Medical School, 373 Plantation Street, Worcester, MA 01605, USA., Doxsey DD; Program in Molecular Medicine, University of Massachusetts Chan Medical School, 373 Plantation Street, Worcester, MA 01605, USA., Veinotte K; Program in Molecular Medicine, University of Massachusetts Chan Medical School, 373 Plantation Street, Worcester, MA 01605, USA., Ouch C; Department of Biochemistry & Molecular Biotechnology, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USA., Chang JY; Department of Biochemistry & Molecular Biotechnology, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USA., Song K; Department of Biochemistry & Molecular Biotechnology, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USA., Xu C; Department of Biochemistry & Molecular Biotechnology, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USA., Shen K; Program in Molecular Medicine, University of Massachusetts Chan Medical School, 373 Plantation Street, Worcester, MA 01605, USA; Department of Biochemistry & Molecular Biotechnology, University of Massachusetts Chan Medical School, 364 Plantation Street, Worcester, MA 01605, USA. Electronic address: kuang.shen@umassmed.edu. |
المصدر: | Structure (London, England : 1993) [Structure] 2023 Sep 07; Vol. 31 (9), pp. 1065-1076.e5. Date of Electronic Publication: 2023 Jul 14. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101087697 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-4186 (Electronic) Linking ISSN: 09692126 NLM ISO Abbreviation: Structure Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2000- : Cambridge, Mass. : Cell Press Original Publication: London : Current Biology, c1993- |
مواضيع طبية MeSH: | Schizosaccharomyces*/genetics , Schizosaccharomyces*/metabolism , Monomeric GTP-Binding Proteins*/chemistry, Humans ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Amino Acids/metabolism |
مستخلص: | mTORC1 is a protein kinase complex that controls cellular growth in response to nutrient availability. Amino acid signals are transmitted toward mTORC1 via the Rag/Gtr GTPases and their upstream regulators. An important regulator is LAMTOR, which localizes Rag/Gtr on the lysosomal/vacuole membrane. In human cells, LAMTOR consists of five subunits, but in yeast, only three or four. Currently, it is not known how variation of the subunit stoichiometry may affect its structural organization and biochemical properties. Here, we report a 3.1 Å-resolution structural model of the Gtr-Lam complex in Schizosaccharomyces pombe. We found that SpGtr shares conserved architecture as HsRag, but the intersubunit communication that coordinates nucleotide loading on the two subunits differs. In contrast, SpLam contains distinctive structural features, but its GTP-specific GEF activity toward SpGtr is evolutionarily conserved. Our results revealed unique evolutionary paths of the protein components of the mTORC1 pathway. Competing Interests: Declaration of interests The authors declare no conflict of interests. (Copyright © 2023 Elsevier Ltd. All rights reserved.) |
References: | Nat Cell Biol. 2008 Aug;10(8):935-45. (PMID: 18604198) Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13571-6. (PMID: 12271141) Nat Rev Mol Cell Biol. 2020 Apr;21(4):183-203. (PMID: 31937935) Cell Discov. 2017 Dec 26;3:17049. (PMID: 29285400) Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501. (PMID: 20383002) Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):861-877. (PMID: 31588918) J Biol Chem. 2023 Jul;299(7):104880. (PMID: 37269949) Curr Opin Cell Biol. 2017 Apr;45:72-82. (PMID: 28411448) Cell. 2012 Sep 14;150(6):1196-208. (PMID: 22980980) Nature. 2018 Apr 5;556(7699):64-69. (PMID: 29590090) Cell Metab. 2017 Aug 1;26(2):301-309. (PMID: 28768171) Mol Cell. 2017 Nov 2;68(3):552-565.e8. (PMID: 29056322) Nat Methods. 2017 Mar;14(3):290-296. (PMID: 28165473) Nat Rev Cancer. 2018 Dec;18(12):744-757. (PMID: 30425336) Nat Cell Biol. 2019 Jan;21(1):63-71. (PMID: 30602761) Methods Enzymol. 2022;675:131-158. (PMID: 36220268) Cell Res. 2015 Sep;25(9):1043-59. (PMID: 26206314) Elife. 2017 Dec 04;6:. (PMID: 29199950) Science. 2019 Oct 11;366(6462):203-210. (PMID: 31601764) Mol Cell Biol. 2004 Sep;24(18):7965-75. (PMID: 15340059) Cell. 2019 Nov 27;179(6):1319-1329.e8. (PMID: 31704029) Nature. 2021 Aug;596(7873):583-589. (PMID: 34265844) Science. 2008 Jun 13;320(5882):1496-501. (PMID: 18497260) Nat Commun. 2017 Nov 20;8(1):1625. (PMID: 29158492) Genes Dev. 2011 Aug 15;25(16):1668-73. (PMID: 21816923) Mol Cell Biol. 2008 Jun;28(12):4104-15. (PMID: 18411301) EMBO J. 2009 Mar 4;28(5):477-89. (PMID: 19177150) Nature. 2017 Dec 21;552(7685):368-373. (PMID: 29236692) Cell. 2014 Feb 13;156(4):771-85. (PMID: 24529379) Science. 2019 Oct 25;366(6464):468-475. (PMID: 31601708) Science. 2017 Oct 20;358(6361):377-381. (PMID: 28935770) Small GTPases. 2022 Jan;13(1):327-334. (PMID: 36328771) Mol Cell. 2022 May 19;82(10):1836-1849.e5. (PMID: 35338845) Sci Adv. 2019 Sep 25;5(9):eaax8164. (PMID: 31579828) Cell. 2010 Apr 16;141(2):290-303. (PMID: 20381137) Nat Metab. 2020 Sep;2(9):893-901. (PMID: 32719541) J Struct Biol. 2005 Oct;152(1):36-51. (PMID: 16182563) J Biol Chem. 2019 Feb 22;294(8):2970-2975. (PMID: 30651352) Elife. 2018 Nov 09;7:. (PMID: 30412051) Nat Commun. 2021 Jan 12;12(1):339. (PMID: 33436626) J Biol Chem. 2012 Aug 24;287(35):29648-53. (PMID: 22807443) Nat Cell Biol. 2003 Jun;5(6):578-81. (PMID: 12771962) Proc Natl Acad Sci U S A. 2018 Sep 18;115(38):9545-9550. (PMID: 30181260) Mol Cell. 2017 Dec 7;68(5):835-846.e3. (PMID: 29107538) J Biol Chem. 2021 Jul;297(1):100861. (PMID: 34116056) |
معلومات مُعتمدة: | R35 GM146824 United States GM NIGMS NIH HHS |
فهرسة مساهمة: | Keywords: GATOR1; Gtr GTPase; LAMTOR; Rag GTPase; mTOR complex 1 (mTORC1); nutrient sensing |
المشرفين على المادة: | EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) 0 (Amino Acids) EC 3.6.5.2 (Monomeric GTP-Binding Proteins) |
تواريخ الأحداث: | Date Created: 20230715 Date Completed: 20230911 Latest Revision: 20231003 |
رمز التحديث: | 20231003 |
مُعرف محوري في PubMed: | PMC10529327 |
DOI: | 10.1016/j.str.2023.06.012 |
PMID: | 37453417 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1878-4186 |
---|---|
DOI: | 10.1016/j.str.2023.06.012 |