7ZBH

ATP-dependent zinc metalloprotease FtsH (BB0789) from Borrelia burgdorferi

Summary for 7ZBH

• Entry DOI: 10.2210/pdb7zbh/pdb
• Descriptor: ATP-dependent zinc metalloprotease FtsH, ADENOSINE-5'-DIPHOSPHATE, ZINC ION (3 entities in total)
• Functional Keywords: lyme disease, borreliosis, metalloprotease., hydrolase
• Biological source: Borreliella burgdorferi B31
• Total number of polymer chains: 6
• Total formula weight: 302478.03

Authors

Brangulis, K. (deposition date: 2022-03-23, release date: 2023-04-05, Last modification date: 2026-02-04)

Primary citation

Brangulis, K.,Drunka, L.,Akopjana, I.,Tars, K.
Structure of the Borrelia burgdorferi ATP-dependent metalloprotease FtsH in its functionally relevant hexameric form.
Biochim Biophys Acta Proteins Proteom, 1872:140969-140969, 2024

PubMed Abstract: ATP-dependent proteases FtsH are conserved in bacteria, mitochondria, and chloroplasts, where they play an essential role in degradation of misfolded/unneeded membrane and cytosolic proteins. It has also been demonstrated that the FtsH homologous protein BB0789 is crucial for mouse and tick infectivity and in vitro growth of the Lyme disease-causing agent Borrelia burgdorferi. This is not surprising, considering B. burgdorferi complex life cycle, residing in both in mammals and ticks, which requires a wide range of membrane proteins and short-lived cytosolic regulatory proteins to invade and persist in the host organism. In the current study, we have solved the crystal structure of the cytosolic BB0789, lacking both N-terminal transmembrane α-helices and the small periplasmic domain. The structure revealed the arrangement of the AAA+ ATPase and the zinc-dependent metalloprotease domains in a hexamer ring, which is essential for ATPase and proteolytic activity. The AAA+ domain was found in an ADP-bound state, while the protease domain showed coordination of a zinc ion by two histidine residues and one aspartic acid residue. The loop region that forms the central pore in the oligomer was poorly defined in the crystal structure and therefore predicted by AlphaFold to complement the missing structural details, providing a complete picture of the functionally relevant hexameric form of BB0789. We confirmed that BB0789 is functionally active, possessing both protease and ATPase activities, thus providing novel structural-functional insights into the protein, which is known to be absolutely necessary for B. burgdorferi to survive and cause Lyme disease.

PubMed: 37852516
DOI: 10.1016/j.bbapap.2023.140969

Experimental method

X-RAY DIFFRACTION (3.3 Å)