8YJA

Structure of Vibrio vulnificus MARTX cysteine protease domain lacking beta-flap

Summary for 8YJA

• Entry DOI: 10.2210/pdb8yja/pdb
• Descriptor: MARTX cysteine protease domain, SODIUM ION, INOSITOL HEXAKISPHOSPHATE, ... (4 entities in total)
• Functional Keywords: protease, inositol hexaphosphate, activation, toxin
• Biological source: Vibrio vulnificus MO6-24/O
• Total number of polymer chains: 2
• Total formula weight: 46040.67

Authors

Chen, L.,Khan, H.,Tan, L.,Li, X.,Zhang, G.,Im, Y.J. (deposition date: 2024-03-01, release date: 2024-07-10, Last modification date: 2024-08-14)

Primary citation

Chen, L.,Khan, H.,Tan, L.,Li, X.,Zhang, G.,Im, Y.J.
Structural basis of the activation of MARTX cysteine protease domain from Vibrio vulnificus.
Plos One, 19:e0307512-e0307512, 2024

PubMed Abstract: The multifunctional autoprocessing repeat-in-toxin (MARTX) toxin is the primary virulence factor of Vibrio vulnificus displaying cytotoxic and hemolytic properties. The cysteine protease domain (CPD) is responsible for activating the MARTX toxin by cleaving the toxin precursor and releasing the mature toxin fragments. To investigate the structural determinants for inositol hexakisphosphate (InsP6)-mediated activation of the CPD, we determined the crystal structures of unprocessed and β-flap truncated MARTX CPDs of Vibrio vulnificus strain MO6-24/O in complex with InsP6 at 1.3 and 2.2Å resolution, respectively. The CPD displays a conserved domain with a central seven-stranded β-sheet flanked by three α-helices. The scissile bond Leu3587-Ala3588 is bound in the catalytic site of the InsP6-loaded form of the Cys3727Ala mutant. InsP6 interacts with the conserved basic cleft and the β-flap inducing the active conformation of catalytic residues. The β-flap of the post-CPD is flexible in the InsP6-unbound state. The structure of the CPD Δβ-flap showed an inactive conformation of the catalytic residues due to the absence of interaction between the active site and the β-flap. This study confirms the InsP6-mediated activation of the MARTX CPDs in which InsP6-binding induces conformational changes of the catalytic residues and the β-flap that holds the N terminus of the CPD in the active site, facilitating hydrolysis of the scissile bond.

PubMed: 39093838
DOI: 10.1371/journal.pone.0307512

Experimental method

X-RAY DIFFRACTION (2.2 Å)