Human endogenous retrovirus K (HERV-K) envelope structures in pre- and post-fusion by Cryo-EM
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
The HERV-K envelope glycoprotein (Env) is aberrantly expressed in diseases including cancers and autoimmune disorders and is targeted by antibodies. The lack of structural information has hindered functional and immune recognition studies. We solved structures of the HERV-K Env in both pre- and post-fusion states with novel monoclonal antibodies using cryo-EM. The pre-fusion Env assembles as a trimer with a distinct fold and architecture compared to other retroviruses, while the post-fusion conformation features a unique “tether” helix within the TM subunit. A panel of monoclonal antibodies, elicited to facilitate structure determination, have been characterized for conformational and subunit specificity, serving as valuable research tools. These findings establish a structural framework for mechanistic studies of HERV-K Env in diseases and evaluation as a potential therapeutic target.
