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High-resolution HDX-MS reveals distinct mechanisms of RNA recognition and activation by RIG-I and MDA5

หน่วยงาน Nanyang Technological University, Singapore

รายละเอียด

ชื่อเรื่อง : High-resolution HDX-MS reveals distinct mechanisms of RNA recognition and activation by RIG-I and MDA5
นักวิจัย : Zheng, Jie , Yong, Hui Yee , Panutdaporn, Nantika , Liu, Chuanfa , Tang, Kai , Luo, Dahai
คำค้น : DRNTU::Science::Biological sciences
หน่วยงาน : Nanyang Technological University, Singapore
ผู้ร่วมงาน : -
ปีพิมพ์ : 2557
อ้างอิง : Zheng, J., Yong, H. Y., Panutdaporn, N., Liu, C., Tang, K., & Luo, D. (2014). High-resolution HDX-MS reveals distinct mechanisms of RNA recognition and activation by RIG-I and MDA5. Nucleic acids research, in press. , 0305-1048 , http://hdl.handle.net/10220/24589 , http://dx.doi.org/10.1093/nar/gku1329
ที่มา : -
ความเชี่ยวชาญ : -
ความสัมพันธ์ : Nucleic acids research
ขอบเขตของเนื้อหา : -
บทคัดย่อ/คำอธิบาย :

RIG-I and MDA5 are the major intracellular immune receptors that recognize viral RNA species and undergo a series of conformational transitions leading to the activation of the interferon-mediated antiviral response. However, to date, full-length RLRs have resisted crystallographic efforts and a molecular description of their activation pathways remains hypothetical. Here we employ hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) to probe the apo states of RIG-I and MDA5 and to dissect the molecular details with respect to distinct RNA species recognition, ATP binding and hydrolysis and CARDs activation. We show that human RIG-I maintains an auto-inhibited resting state owing to the intra-molecular HEL2i-CARD2 interactions while apo MDA5 lacks the analogous intra-molecular interactions and therefore adopts an extended conformation. Our work demonstrates that RIG-I binds and responds differently to short triphosphorylated RNA and long duplex RNA and that sequential addition of RNA and ATP triggers specific allosteric effects leading to RIG-I CARDs activation. We also present a high-resolution protein surface mapping technique that refines the cooperative oligomerization model of neighboring MDA5 molecules on long duplex RNA. Taken together, our data provide a high-resolution view of RLR activation in solution and offer new evidence for the molecular mechanism of RLR activation.

บรรณานุกรม :
Zheng, Jie , Yong, Hui Yee , Panutdaporn, Nantika , Liu, Chuanfa , Tang, Kai , Luo, Dahai . (2557). High-resolution HDX-MS reveals distinct mechanisms of RNA recognition and activation by RIG-I and MDA5.
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Zheng, Jie , Yong, Hui Yee , Panutdaporn, Nantika , Liu, Chuanfa , Tang, Kai , Luo, Dahai . 2557. "High-resolution HDX-MS reveals distinct mechanisms of RNA recognition and activation by RIG-I and MDA5".
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Zheng, Jie , Yong, Hui Yee , Panutdaporn, Nantika , Liu, Chuanfa , Tang, Kai , Luo, Dahai . "High-resolution HDX-MS reveals distinct mechanisms of RNA recognition and activation by RIG-I and MDA5."
    กรุงเทพมหานคร : Nanyang Technological University, Singapore, 2557. Print.
Zheng, Jie , Yong, Hui Yee , Panutdaporn, Nantika , Liu, Chuanfa , Tang, Kai , Luo, Dahai . High-resolution HDX-MS reveals distinct mechanisms of RNA recognition and activation by RIG-I and MDA5. กรุงเทพมหานคร : Nanyang Technological University, Singapore; 2557.