Structural basis for the unfolding of anthrax lethal factor by protective antigen oligomers. 2010

Geoffrey K Feld, and Katie L Thoren, and Alexander F Kintzer, and Harry J Sterling, and Iok I Tang, and Shoshana G Greenberg, and Evan R Williams, and Bryan A Krantz
Department of Chemistry, University of California, Berkeley, California, USA.

The protein transporter anthrax lethal toxin is composed of protective antigen (PA), a transmembrane translocase, and lethal factor (LF), a cytotoxic enzyme. After its assembly into holotoxin complexes, PA forms an oligomeric channel that unfolds LF and translocates it into the host cell. We report the crystal structure of the core of a lethal toxin complex to 3.1-Å resolution; the structure contains a PA octamer bound to four LF PA-binding domains (LF(N)). The first α-helix and β-strand of each LF(N) unfold and dock into a deep amphipathic cleft on the surface of the PA octamer, which we call the α clamp. The α clamp possesses nonspecific polypeptide binding activity and is functionally relevant to efficient holotoxin assembly, PA octamer formation, and LF unfolding and translocation. This structure provides insight into the mechanism of translocation-coupled protein unfolding.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D000942 Antigens, Bacterial Substances elaborated by bacteria that have antigenic activity. Bacterial Antigen,Bacterial Antigens,Antigen, Bacterial
D001408 Bacillus anthracis A species of bacteria that causes ANTHRAX in humans and animals.
D001427 Bacterial Toxins Toxic substances formed in or elaborated by bacteria; they are usually proteins with high molecular weight and antigenicity; some are used as antibiotics and some to skin test for the presence of or susceptibility to certain diseases. Bacterial Toxin,Toxins, Bacterial,Toxin, Bacterial
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D017434 Protein Structure, Tertiary The level of protein structure in which combinations of secondary protein structures (ALPHA HELICES; BETA SHEETS; loop regions, and AMINO ACID MOTIFS) pack together to form folded shapes. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Tertiary Protein Structure,Protein Structures, Tertiary,Tertiary Protein Structures
D058767 Protein Unfolding Conformational transitions of the shape of a protein to various unfolded states. Unfolding, Protein
D021381 Protein Transport The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport. Cellular Protein Targeting,Gated Protein Transport,Protein Targeting, Cellular,Protein Translocation,Transmembrane Protein Transport,Vesicular Protein Transport,Protein Localization Processes, Cellular,Protein Sorting,Protein Trafficking,Protein Transport, Gated,Protein Transport, Transmembrane,Protein Transport, Vesicular,Traffickings, Protein
D025941 Protein Interaction Mapping Methods for determining interaction between PROTEINS. Interaction Mapping, Protein,Interaction Mappings, Protein,Mapping, Protein Interaction,Mappings, Protein Interaction,Protein Interaction Mappings

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