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-Structure paper
タイトル | Structure of Cya, an evolutionary ancestor of the mammalian membrane adenylyl cyclases. |
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ジャーナル・号・ページ | Elife, Vol. 11, Year 2022 |
掲載日 | 2022年8月18日 |
著者 | Ved Mehta / Basavraj Khanppnavar / Dina Schuster / Ilayda Kantarci / Irene Vercellino / Angela Kosturanova / Tarun Iype / Sasa Stefanic / Paola Picotti / Volodymyr M Korkhov / |
PubMed 要旨 | adenylyl cyclase (AC) Rv1625c/Cya is an evolutionary ancestor of the mammalian membrane ACs and a model system for studies of their structure and function. Although the vital role of ACs in cellular ... adenylyl cyclase (AC) Rv1625c/Cya is an evolutionary ancestor of the mammalian membrane ACs and a model system for studies of their structure and function. Although the vital role of ACs in cellular signalling is well established, the function of their transmembrane (TM) regions remains unknown. Here, we describe the cryo-EM structure of Cya bound to a stabilizing nanobody at 3.6 Å resolution. The TM helices 1-5 form a structurally conserved domain that facilitates the assembly of the helical and catalytic domains. The TM region contains discrete pockets accessible from the extracellular and cytosolic side of the membrane. Neutralization of the negatively charged extracellular pocket Ex1 destabilizes the cytosolic helical domain and reduces the catalytic activity of the enzyme. The TM domain acts as a functional component of Cya, guiding the assembly of the catalytic domain and providing the means for direct regulation of catalytic activity in response to extracellular ligands. |
リンク | Elife / PubMed:35980026 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.97 - 3.83 Å |
構造データ | EMDB-14388, PDB-7yzi: EMDB-14389, PDB-7yzk: PDB-7yz9: |
化合物 | ChemComp-MN: ChemComp-GOL: ChemComp-ONM: ChemComp-HOH: |
由来 |
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キーワード | SIGNALING PROTEIN / Membrane Adenylyl Cyclase / Nanobody / Complex / Mycobacterium Tuberculosis / MEMBRANE PROTEIN / Adenylyl cyclase / cyclic adenosine monophosphate / signal transduction |