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TitleStructure of Cya, an evolutionary ancestor of the mammalian membrane adenylyl cyclases.
Journal, issue, pagesElife, Vol. 11, Year 2022
Publish dateAug 18, 2022
AuthorsVed Mehta / Basavraj Khanppnavar / Dina Schuster / Ilayda Kantarci / Irene Vercellino / Angela Kosturanova / Tarun Iype / Sasa Stefanic / Paola Picotti / Volodymyr M Korkhov /
PubMed Abstract 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.
External linksElife / PubMed:35980026 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.97 - 3.83 Å
Structure data

EMDB-14388, PDB-7yzi:
Structure of Mycobacterium tuberculosis adenylyl cyclase Rv1625c / Cya
Method: EM (single particle) / Resolution: 3.83 Å

EMDB-14389, PDB-7yzk:
Structure of Mycobacterium tuberculosis adenylyl cyclase Rv1625c / Cya
Method: EM (single particle) / Resolution: 3.57 Å

PDB-7yz9:
Structure of catalytic domain of Rv1625c bound to nanobody NB4
Method: X-RAY DIFFRACTION / Resolution: 1.97 Å

Chemicals

ChemComp-MN:
Unknown entry

ChemComp-GOL:
GLYCEROL

ChemComp-ONM:
3'-O-(N-METHYLANTHRANILOYL)-GUANOSINE-5'-TRIPHOSPHATE

ChemComp-HOH:
WATER

Source
  • mycobacterium tuberculosis '98-r604 inh-rif-em' (bacteria)
  • vicugna pacos (alpaca)
  • mycobacterium tuberculosis (bacteria)
  • mycobacterium tuberculosis h37rv (bacteria)
KeywordsSIGNALING PROTEIN / Membrane Adenylyl Cyclase / Nanobody / Complex / Mycobacterium Tuberculosis / MEMBRANE PROTEIN / Adenylyl cyclase / cyclic adenosine monophosphate / signal transduction

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