Structures of the Insecticidal Toxin Complex Subunit XptA2 Highlight Roles for Flexible Domains.

Autor: Martin CL; Department of Pharmacology & Toxicology, University of Alabama at Birmingham, Birmingham, AL 35205, USA., Chester DW; Department of Pharmacology & Toxicology, University of Alabama at Birmingham, Birmingham, AL 35205, USA., Radka CD; Department of Pharmacology & Toxicology, University of Alabama at Birmingham, Birmingham, AL 35205, USA.; Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY 40536, USA., Pan L; Department of Pharmacology & Toxicology, University of Alabama at Birmingham, Birmingham, AL 35205, USA., Yang Z; Department of Biochemistry & Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35205, USA., Hart RC; Department of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Binshtein EM; Department of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Wang Z; Biochemistry & Molecular Pharmacology, Cryo-Electron Microscopy and Tomography Core, Baylor College of Medicine, Houston, TX 77030, USA., Nagy L; Department of Mathematics, Engineering & Physical Sciences, Jefferson State Community College, Jefferson Campus, Birmingham, AL 35215, USA., DeLucas LJ; Predictive Oncology Inc., 200 Riverhills Business Park, Suite 250, Birmingham, AL 35242, USA., Aller SG; Department of Pharmacology & Toxicology, University of Alabama at Birmingham, Birmingham, AL 35205, USA.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Aug 25; Vol. 24 (17). Date of Electronic Publication: 2023 Aug 25.
DOI: 10.3390/ijms241713221
Abstrakt: The Toxin Complex (Tc) superfamily consists of toxin translocases that contribute to the targeting, delivery, and cytotoxicity of certain pathogenic Gram-negative bacteria. Membrane receptor targeting is driven by the A-subunit (TcA), which comprises IgG-like receptor binding domains (RBDs) at the surface. To better understand XptA2, an insect specific TcA secreted by the symbiont X. nematophilus from the intestine of entomopathogenic nematodes, we determined structures by X-ray crystallography and cryo-EM. Contrary to a previous report, XptA2 is pentameric. RBD-B exhibits an indentation from crystal packing that indicates loose association with the shell and a hotspot for possible receptor binding or a trigger for conformational dynamics. A two-fragment XptA2 lacking an intact linker achieved the folded pre-pore state like wild type (wt), revealing no requirement of the linker for protein folding. The linker is disordered in all structures, and we propose it plays a role in dynamics downstream of the initial pre-pore state.
Databáze: MEDLINE
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