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-Structure paper
タイトル | Sec7 regulatory domains scaffold autoinhibited and active conformations. |
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ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 121, Issue 10, Page e2318615121, Year 2024 |
掲載日 | 2024年3月5日 |
著者 | Bryce A Brownfield / Brian C Richardson / Steve L Halaby / J Christopher Fromme / |
PubMed 要旨 | The late stages of Golgi maturation involve a series of sequential trafficking events in which cargo-laden vesicles are produced and targeted to multiple distinct subcellular destinations. Each of ...The late stages of Golgi maturation involve a series of sequential trafficking events in which cargo-laden vesicles are produced and targeted to multiple distinct subcellular destinations. Each of these vesicle biogenesis events requires activation of an Arf GTPase by the Sec7/BIG guanine nucleotide exchange factor (GEF). Sec7 localization and activity is regulated by autoinhibition, positive feedback, and interaction with other GTPases. Although these mechanisms have been characterized biochemically, we lack a clear picture of how GEF localization and activity is modulated by these signals. Here, we report the cryogenic electron microscopy structure of full-length Sec7 in its autoinhibited form, revealing the architecture of its multiple regulatory domains. We use functional experiments to determine the basis for autoinhibition and use structural predictions to produce a model for an active conformation of the GEF that is supported empirically. This study therefore elucidates the conformational transition that Sec7 undergoes to become active on the organelle membrane surface. |
リンク | Proc Natl Acad Sci U S A / PubMed:38416685 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.7 - 5.3 Å |
構造データ | EMDB-42135, PDB-8ucq: EMDB-42182: Focused map of Sec7 monomer autoinhibited conformation EMDB-42183: Consensus map of Sec7 dimer autoinhibited conformation |
由来 |
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キーワード | PROTEIN TRANSPORT / GEF / Exchange Factor / Golgi |