title: Structure of Ptr ToxA: an RGD-containing host-selective toxin from Pyrenophora tritici-repentis.
abstract: Tan spot of wheat (Triticum aestivum), caused by the fungus Pyrenophora tritici-repentis, has significant agricultural and economic impact. Ptr ToxA (ToxA), the first discovered proteinaceous host-selective toxin, is produced by certain P. tritici-repentis races and is necessary and sufficient to cause cell death in sensitive wheat cultivars. We present here the high-resolution crystal structure of ToxA in two different crystal forms, providing four independent views of the protein. ToxA adopts a single-domain, beta-sandwich fold of novel topology. Mapping of the existing mutation data onto the structure supports the hypothesized importance of an Arg-Gly-Asp (RGD) and surrounding sequence. Its occurrence in a single, solvent-exposed loop in the protein suggests that it is directly involved in recognition events required for ToxA action. Furthermore, the ToxA structure reveals a surprising similarity with the classic mammalian RGD-containing domain, the fibronectin type III (FnIII) domain: the two topologies are related by circular permutation. The similar topologies and the positional conservation of the RGD-containing loop raises the possibility that ToxA is distantly related to mammalian FnIII proteins and that to gain entry it binds to an integrin-like receptor in the plant host.
authors.affiliation: Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331, USA.
authors.forename: Ganapathy N
authors.initials: GN
authors.lastname: Sarma
authors.forename: Viola A
authors.initials: VA
authors.lastname: Manning
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Ciuffetti
authors.forename: P Andrew
authors.initials: PA
authors.lastname: Karplus
mesh_terms: D000595:Amino Acid Sequence / Q000502:physiology; D017124:Conserved Sequence / Q000502:physiology; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D005353:Fibronectins / Q000737:chemistry; D005656:Fungal Proteins / Q000737:chemistry*; D005658:Fungi / Q000737:chemistry* / Q000378:metabolism*; D006790:Host-Parasite Interactions / Q000502:physiology; D008958:Models, Molecular; D009181:Mycoses / Q000382:microbiology*; D009183:Mycotoxins / Q000737:chemistry*; D010802:Phylogeny; D010935:Plant Diseases / Q000382:microbiology*; D020836:Protein Structure, Quaternary / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D014908:Triticum / Q000382:microbiology*
chemical_list: D005353:Fibronectins; D005656:Fungal Proteins; D009183:Mycotoxins; C105776:TOXA protein, Pyrenophora tritici-repentis