Opitz Syndrome
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Findings from University of Geneva in life sciences reported
2009 MAY 11 - (NewsRx.com) -- "TRIM5 alpha is a retrovirus restriction factor in the host cell cytoplasm that blocks infection before provirus establishment. Restriction activity requires capsid (CA)-specific recognition by the PRYSPRY domain of TRIM5 alpha," scientists in Geneva, Switzerland report. "To better understand the restriction mechanism, nine charge-cluster-to-triple-alanine mutants in the TRIM5 alpha PRYSPRY domain were assessed for CA-specific restriction activity. Five mutants distributed along the TRIM5 alpha PRYSPRY primary sequence disrupted restriction activity against N-tropic murine leukemia virus and equine infectious anemia virus. Modeling of the TRIM5 alpha PRYSPRY domain based on the crystal structures of PRYSPRY-19q13.4.1, GUSTAVUS, and TRIM21 identified a surface patch where disruptive mutants clustered. All mutants in this patch retained CA-binding activity, a reticular distribution in the cytoplasm, and steady-state protein levels comparable to those of the wild type. Residues in the essential patch are conserved in TRIM5 alpha orthologues and in closely related paralogues. The same surface patch in the TRIM18 and TRIM20 PRYSPRY domains is the site of mutants causing Opitz syndrome and familial Mediterranean fever," wrote S. Sebastian and colleagues, University of Geneva. The researchers concluded: "These results indicate that, in addition to CA-specific binding, the PRYSPRY domain possesses a second function, possibly binding of a cofactor, that is essential for retroviral restriction activity by TRIM5 alpha." Sebastian and colleagues published their study in the Journal of Virology (An Invariant Surface Patch on the TRIM5 alpha PRYSPRY Domain Is Required for Retroviral Restriction but Dispensable for Capsid Binding. Journal of Virology, 2009;83(7):3365-3373). For additional information, contact J. Luban, University of Geneva, Dept. of Microbiology & Molecular Medical, CH-1211 Geneva, Switzerland. The publisher's contact information for the Journal of Virology is: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA. Keywords: Switzerland, Geneva, Life Sciences, Hematology, Oncology, Leukemia, Retrovirus, Provirus, Virology, Viral Research, Murine Leukemia Virus, University of Geneva. This article was prepared by Hematology Week editors from staff and other reports. Copyright 2009, Hematology Week via NewsRx.com.
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