Show simple item record

dc.contributor.authorShen, Kuang
dc.contributor.authorRogala, Kacper B.
dc.contributor.authorChou, Hui-Ting
dc.contributor.authorHuang, Rick K.
dc.contributor.authorYu, Zhiheng
dc.contributor.authorSabatini, David M.
dc.date2022-08-11T08:10:18.000
dc.date.accessioned2022-08-23T17:03:20Z
dc.date.available2022-08-23T17:03:20Z
dc.date.issued2019-11-27
dc.date.submitted2020-02-06
dc.identifier.citation<p>Shen K, Rogala KB, Chou HT, Huang RK, Yu Z, Sabatini DM. Cryo-EM Structure of the Human FLCN-FNIP2-Rag-Ragulator Complex. <em>Cell</em>. 2019 Nov 27;179(6):1319-1329.e8. doi: 10.1016/j.cell.2019.10.036. Epub 2019 Nov 6. PMID: 31704029. <a href="https://doi.org/10.1016/j.cell.2019.10.036">Link to article on publisher's site</a></p>
dc.identifier.issn0092-8674 (Linking)
dc.identifier.doi10.1016/j.cell.2019.10.036
dc.identifier.pmid31704029
dc.identifier.urihttp://hdl.handle.net/20.500.14038/44402
dc.description.abstractmTORC1 controls anabolic and catabolic processes in response to nutrients through the Rag GTPase heterodimer, which is regulated by multiple upstream protein complexes. One such regulator, FLCN-FNIP2, is a GTPase activating protein (GAP) for RagC/D, but despite its important role, how it activates the Rag GTPase heterodimer remains unknown. We used cryo-EM to determine the structure of FLCN-FNIP2 in a complex with the Rag GTPases and Ragulator. FLCN-FNIP2 adopts an extended conformation with two pairs of heterodimerized domains. The Longin domains heterodimerize and contact both nucleotide binding domains of the Rag heterodimer, while the DENN domains interact at the distal end of the structure. Biochemical analyses reveal a conserved arginine on FLCN as the catalytic arginine finger and lead us to interpret our structure as an on-pathway intermediate. These data reveal features of a GAP-GTPase interaction and the structure of a critical component of the nutrient-sensing mTORC1 pathway.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31704029&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1016/j.cell.2019.10.036
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBiochemistry
dc.subjectMolecular Biology
dc.subjectMolecular Genetics
dc.subjectNucleic Acids, Nucleotides, and Nucleosides
dc.titleCryo-EM Structure of the Human FLCN-FNIP2-Rag-Ragulator Complex
dc.typeJournal Article
dc.source.journaltitleCell
dc.source.volume179
dc.source.issue6
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/pmm_pp/136
dc.identifier.contextkey16469699
html.description.abstract<p>mTORC1 controls anabolic and catabolic processes in response to nutrients through the Rag GTPase heterodimer, which is regulated by multiple upstream protein complexes. One such regulator, FLCN-FNIP2, is a GTPase activating protein (GAP) for RagC/D, but despite its important role, how it activates the Rag GTPase heterodimer remains unknown. We used cryo-EM to determine the structure of FLCN-FNIP2 in a complex with the Rag GTPases and Ragulator. FLCN-FNIP2 adopts an extended conformation with two pairs of heterodimerized domains. The Longin domains heterodimerize and contact both nucleotide binding domains of the Rag heterodimer, while the DENN domains interact at the distal end of the structure. Biochemical analyses reveal a conserved arginine on FLCN as the catalytic arginine finger and lead us to interpret our structure as an on-pathway intermediate. These data reveal features of a GAP-GTPase interaction and the structure of a critical component of the nutrient-sensing mTORC1 pathway.</p>
dc.identifier.submissionpathpmm_pp/136
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages1319-1329.e8


Files in this item

Thumbnail
Name:
Publisher version

This item appears in the following Collection(s)

Show simple item record