ArticleNature communications2022
Structural basis of adenylyl cyclase 9 activation.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- The evolutionary conservation of eukaryotic membrane-bound adenylyl cyclase isoforms.Frontiers in pharmacology · 2022Pooled it
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- Lipid regulation of adenylyl cyclase Rv1625c from Mycobacterium tuberculosis by its membrane-domain receptor.The FEBS journal · 2025Article
- A signal transduction blind spot: the function of adenylyl cyclase transmembrane domains.The FEBS journal · 2025Review
- A New Adjuvant Treatment for Glioblastoma Using Aprepitant, Vortioxetine, Roflumilast and Olanzapine: The AVRO Regimen.International journal of molecular sciences · 2025Review
- Article
- Role and Interplay of Different Signaling Pathways Involved in Sciatic Nerve Regeneration.Journal of molecular neuroscience : MN · 2024Review
- Biochemical pharmacology of adenylyl cyclases in cancer.Biochemical pharmacology · 2024Review
- A designed ankyrin-repeat protein that targets Parkinson's disease-associated LRRK2.The Journal of biological chemistry · 2024Article
- Real-Time Determination of Intracellular cAMP Reveals Functional Coupling of GInternational journal of molecular sciences · 2024Article
- Regulatory sites of CaM-sensitive adenylyl cyclase AC8 revealed by cryo-EM and structural proteomics.EMBO reports · 2024Article
- Dissecting the molecular basis for the modulation of neurotransmitter GPCR signaling by GINIP.Structure (London, England : 1993) · 2024Article
- The mechanism ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Alcohol, White Adipose Tissue, and Brown Adipose Tissue: Mechanistic Links to Lipogenesis and Lipolysis.Nutrients · 2023Review
- Human adenylyl cyclase 9 is auto-stimulated by its isoform-specific C-terminal domain.Life science alliance · 2023Article
- Comparative Analyses Reveal the Genetic Mechanism of Ambergris Production in the Sperm Whale Based on the Chromosome-Level Genome.Animals : an open access journal from MDPI · 2023Article
- Urinary ATP Levels Are Controlled by Nucleotidases Released from the Urothelium in a Regulated Manner.Metabolites · 2022Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
Abstract
Adenylyl cyclase 9 (AC9) is a membrane-bound enzyme that converts ATP into cAMP. The enzyme is weakly activated by forskolin, fully activated by the G protein Gαs subunit and is autoinhibited by the AC9 C-terminus. Although our recent structural studies of the AC9-Gαs complex provided the framework for understanding AC9 autoinhibition, the conformational changes that AC9 undergoes in response to activator binding remains poorly understood. Here, we present the cryo-EM structures of AC9 in several distinct states: (i) AC9 bound to a nucleotide inhibitor MANT-GTP, (ii) bound to an artificial activator (DARPin C4) and MANT-GTP, (iii) bound to DARPin C4 and a nucleotide analogue ATPαS, (iv) bound to Gαs and MANT-GTP. The artificial activator DARPin C4 partially activates AC9 by binding at a site that overlaps with the Gαs binding site. Together with the previously observed occluded and forskolin-bound conformations, structural comparisons of AC9 in the four conformations described here show that secondary structure rearrangements in the region surrounding the forskolin binding site are essential for AC9 activation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.