کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2038558 1072378 2006 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Yersinia Virulence Depends on Mimicry of Host Rho-Family Nucleotide Dissociation Inhibitors
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوشیمی، ژنتیک و زیست شناسی مولکولی (عمومی)
پیش نمایش صفحه اول مقاله
Yersinia Virulence Depends on Mimicry of Host Rho-Family Nucleotide Dissociation Inhibitors
چکیده انگلیسی

SummaryYersinia spp. cause gastroenteritis and the plague, representing historically devastating pathogens that are currently an important biodefense and antibiotic resistance concern. A critical virulence determinant is the Yersinia protein kinase A, or YpkA, a multidomain protein that disrupts the eukaryotic actin cytoskeleton. Here we solve the crystal structure of a YpkA-Rac1 complex and find that YpkA possesses a Rac1 binding domain that mimics host guanidine nucleotide dissociation inhibitors (GDIs) of the Rho GTPases. YpkA inhibits nucleotide exchange in Rac1 and RhoA, and mutations that disrupt the YpkA-GTPase interface abolish this activity in vitro and impair in vivo YpkA-induced cytoskeletal disruption. In cell culture experiments, the kinase and the GDI domains of YpkA act synergistically to promote cytoskeletal disruption, and a Y. pseudotuberculosis mutant lacking YpkA GDI activity shows attenuated virulence in a mouse infection assay. We conclude that virulence in Yersinia depends strongly upon mimicry of host GDI proteins by YpkA.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 126, Issue 5, 8 September 2006, Pages 869–880
نویسندگان
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