7YZ9

Structure of catalytic domain of Rv1625c bound to nanobody NB4

Summary for 7YZ9

• Entry DOI: 10.2210/pdb7yz9/pdb
• Descriptor: Adenylate cyclase, nanobody NB4, MANGANESE (II) ION, ... (6 entities in total)
• Functional Keywords: membrane adenylyl cyclase, nanobody, complex, mycobacterium tuberculosis, signaling protein
• Biological source: Mycobacterium tuberculosis H37Rv; More
• Total number of polymer chains: 2
• Total formula weight: 42979.31

Authors

Khanppnavar, B.,Mehta, V.J.,Iype, T.,Korkhov, V.M. (deposition date: 2022-02-19, release date: 2022-08-31, Last modification date: 2024-11-13)

Primary citation

Mehta, V.,Khanppnavar, B.,Schuster, D.,Kantarci, I.,Vercellino, I.,Kosturanova, A.,Iype, T.,Stefanic, S.,Picotti, P.,Korkhov, V.M.
Structure of Mycobacterium tuberculosis Cya, an evolutionary ancestor of the mammalian membrane adenylyl cyclases.
Elife, 11:-, 2022

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 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.

PubMed: 35980026
DOI: 10.7554/eLife.77032

Experimental method

X-RAY DIFFRACTION (1.97 Å)