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. |
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| 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.) |
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| 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 |
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| DOI: | 10.1016/j.str.2023.06.012 |