کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8324879 | 1539922 | 2012 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Molecular analysis of Plasmodium falciparum co-chaperone Aha1 supports its interaction with and regulation of Hsp90 in the malaria parasite
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کلمات کلیدی
His6ADPco-chaperonePDBNi-NTAGSTAha15-FOAHSP90nuclear magnetic resonance - رزونانس مغناطیسی هستهایDNA - DNA یا اسید دزوکسی ریبونوکلئیکSDS–PAGE - SDS-PAGEAdenosine Triphosphate - آدنوزین تری فسفاتATP - آدنوزین تری فسفات یا ATPadenosine diphosphate - آدنوزین دی فسفات5-fluoroorotic acid - اسید 5-فلوروروتیکdeoxyribonucleic acid - اسید deoxyribonucleicsodium dodecyl sulfate–polyacrylamide gel electrophoresis - الکتروفورز ژل دوده سولفات سدیم پلی آکریل آمیدNMR - تشدید مغناطیسی هستهای Cub - تولهMalaria - مالاریاNub - نوبتwild-type - نوع وحشیnickel-nitrilotriacetic acid - نیکل نیتریلوتوریکات اسیدpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازProtein Data Bank - پروتئین بانک اطلاعاتیHeat shock protein 90 - پروتئین شوک حرارت 90Plasmodium falciparum - پلاسمودیوم فالسیپارومglutathione S-transferase - گلوتاتیون S-ترانسفراز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
The recent recognition of Plasmodium falciparum Hsp90 (PfHsp90) as a promising anti-malaria drug target has sparked interest in identifying factors that regulate its function and drug-interaction. Co-chaperones are well-known regulators of Hsp90's chaperone function, and certain members have been implicated in conferring protection against lethal cellular effects of Hsp90-specific inhibitors. In this context, studies on PfHsp90's co-chaperones are imperative to gain insight into the regulation of the chaperone in the malaria parasite. In this study, a putative co-chaperone P. falciparum Aha1 (PfAha1) was identified and investigated for its interaction and regulation of PfHsp90. A previous genome-wide yeast two-hybrid study failed to identify PfAha1's association with PfHsp90, which prompted us to use a directed assay to investigate their interaction. PfAha1 was shown to interact with PfHsp90 via the in vivo split-ubiquitin assay and the association was confirmed in vitro by GST pull-down experiments. The GST pull-down assay further revealed PfAha1's interaction with PfHsp90 to be dependent on MgCl2 and ATP, and was competed by co-chaperone Pfp23 that binds PfHsp90 under the same condition. In addition, the PfHsp90-PfAha1 complex was found to be sensitive to disruption by high salt, indicating a polar interaction between them. Using bio-computational modelling coupled with site-directed mutagenesis, the polar residue N108 in PfAha1 was found to be strategically located and essential for PfHsp90 interaction. The functional significance of PfAha1's interaction was clearly that of exerting a stimulatory effect on the ATPase activity of PfHsp90, likely to be essential for promoting the activation of PfHsp90's client proteins.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 44, Issue 1, January 2012, Pages 233-245
Journal: The International Journal of Biochemistry & Cell Biology - Volume 44, Issue 1, January 2012, Pages 233-245
نویسندگان
Chun Song Chua, Huiyu Low, Norbert Lehming, T.S. Sim,