1kpt
From Proteopedia
(New page: 200px<br /><applet load="1kpt" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kpt, resolution 1.75Å" /> '''STRUCTURE AND FUNCTI...) |
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caption="1kpt, resolution 1.75Å" /> | caption="1kpt, resolution 1.75Å" /> | ||
'''STRUCTURE AND FUNCTION OF A VIRALLY ENCODED FUNGAL TOXIN FROM USTILAGO MAYDIS: A FUNGAL AND MAMMALIAN CALCIUM CHANNEL INHIBITOR'''<br /> | '''STRUCTURE AND FUNCTION OF A VIRALLY ENCODED FUNGAL TOXIN FROM USTILAGO MAYDIS: A FUNGAL AND MAMMALIAN CALCIUM CHANNEL INHIBITOR'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: The P4 strain of the corn smut fungus, Ustilago maydis, secretes a fungal toxin, KP4, encoded by a fungal virus (UMV4) that | + | BACKGROUND: The P4 strain of the corn smut fungus, Ustilago maydis, secretes a fungal toxin, KP4, encoded by a fungal virus (UMV4) that persistently infects its cells. UMV4, unlike most other (non-fungal) viruses, does not spread to uninfected cells by release into the extracellular milieu during its normal life cycle and is thus dependent upon host survival for replication. In symbiosis with the host fungus, UMV4 encodes KP4 to kill other competitive strains of U. maydis, thereby promoting both host and virus survival. KP4 belongs to a family of fungal toxins and determining its structure should lead to a better understanding of the function and evolutionary origins of these toxins. Elucidation of the mechanism of toxin action could lead to new anti-fungal agents against human pathogens. RESULTS: We have determined the atomic structure of KP4 to 1.9 A resolution. KP4 belongs to the alpha/beta-sandwich family, and has a unique topology comprising a five-stranded antiparallel beta-sheet with two antiparallel alpha-helices lying at approximately 45 degrees to these strands. The structure has two left-handed beta alpha beta cross-overs and a basic protuberance extending from the beta-sheet. In vivo experiments demonstrated abrogation of toxin killing by Ca2+ and, to a lesser extent, Mg2+. These results led to experiments demonstrating that the toxin specifically inhibits voltage-gated Ca2+ channels in mammalian cells. CONCLUSIONS: Similarities, although somewhat limited, between KP4 and scorpion toxins led us to investigate the possibility that the toxic effects of KP4 may be mediated by inhibition of cation channels. Our results suggest that certain properties of fungal Ca2+ channels are homologous to those in mammalian cells. KP4 may, therefore, be a new tool for studying mammalian Ca2+ channels and current mammalian Ca2+ channel inhibitors may be useful lead compounds for new anti-fungal agents. |
==About this Structure== | ==About this Structure== | ||
| - | 1KPT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Ustilago_maydis Ustilago maydis]. Full crystallographic information is available from [http:// | + | 1KPT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Ustilago_maydis Ustilago maydis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KPT OCA]. |
==Reference== | ==Reference== | ||
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[[Category: virally encoded]] | [[Category: virally encoded]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:36:42 2008'' |
Revision as of 11:36, 21 February 2008
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STRUCTURE AND FUNCTION OF A VIRALLY ENCODED FUNGAL TOXIN FROM USTILAGO MAYDIS: A FUNGAL AND MAMMALIAN CALCIUM CHANNEL INHIBITOR
Overview
BACKGROUND: The P4 strain of the corn smut fungus, Ustilago maydis, secretes a fungal toxin, KP4, encoded by a fungal virus (UMV4) that persistently infects its cells. UMV4, unlike most other (non-fungal) viruses, does not spread to uninfected cells by release into the extracellular milieu during its normal life cycle and is thus dependent upon host survival for replication. In symbiosis with the host fungus, UMV4 encodes KP4 to kill other competitive strains of U. maydis, thereby promoting both host and virus survival. KP4 belongs to a family of fungal toxins and determining its structure should lead to a better understanding of the function and evolutionary origins of these toxins. Elucidation of the mechanism of toxin action could lead to new anti-fungal agents against human pathogens. RESULTS: We have determined the atomic structure of KP4 to 1.9 A resolution. KP4 belongs to the alpha/beta-sandwich family, and has a unique topology comprising a five-stranded antiparallel beta-sheet with two antiparallel alpha-helices lying at approximately 45 degrees to these strands. The structure has two left-handed beta alpha beta cross-overs and a basic protuberance extending from the beta-sheet. In vivo experiments demonstrated abrogation of toxin killing by Ca2+ and, to a lesser extent, Mg2+. These results led to experiments demonstrating that the toxin specifically inhibits voltage-gated Ca2+ channels in mammalian cells. CONCLUSIONS: Similarities, although somewhat limited, between KP4 and scorpion toxins led us to investigate the possibility that the toxic effects of KP4 may be mediated by inhibition of cation channels. Our results suggest that certain properties of fungal Ca2+ channels are homologous to those in mammalian cells. KP4 may, therefore, be a new tool for studying mammalian Ca2+ channels and current mammalian Ca2+ channel inhibitors may be useful lead compounds for new anti-fungal agents.
About this Structure
1KPT is a Single protein structure of sequence from Ustilago maydis. Full crystallographic information is available from OCA.
Reference
Structure and function of a virally encoded fungal toxin from Ustilago maydis: a fungal and mammalian Ca2+ channel inhibitor., Gu F, Khimani A, Rane SG, Flurkey WH, Bozarth RF, Smith TJ, Structure. 1995 Aug 15;3(8):805-14. PMID:7582897
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