Affiliation:
1. Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China
2. Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou 510060, China
Abstract
Yellow fever virus (YFV) infections can cause severe diseases in humans, resulting in mass casualties in Africa and the Americas each year. Secretory NS1 (sNS1) is thought to be used as a diagnostic marker of flavivirus infections, playing an essential role in the flavivirus life cycle, but little is known about the composition and structure of YFV sNS1. Here, we present that the recombinant YFV sNS1 exists in a heterogeneous mixture of oligomerizations, predominantly in the tetrameric form. The cryoEM structures show that the YFV tetramer of sNS1 is stacked by the hydrophobic interaction between β-roll domains and greasy fingers. According to the 3D variability analysis, the tetramer is in a semi-stable state that may contain multiple conformations with dynamic changes. We believe that our study provides critical insights into the oligomerization of NS1 and will aid the development of NS1-based diagnoses and therapies.
Funder
Shenzhen Science and Technology Innovation Committee
Shenzhen-Hong Kong Cooperation Zone for Technology and Innovation
Kobilka Institute of Innovative Drug Discovery and Presidential Fellowship and University Development Fund at the Chinese University of Hong Kong, Shenzhen
Presidential Fellowship at the Chinese University of Hong Kong, Shenzhen
Ganghong Young Scholar Development Fund