If a cell were a room, the cell-surface receptors would be the “doorknob” for virus entry. After unlocking the doorknob, viruses can infect the human cells. Previous research has found that the key for the coronavirus to infect human cells is to use the Spike protein of SARS-CoV-2, which can bind to the cellular receptor ACE2. Here, ACE2 is equivalent to the “doorknob” exploited by the coronavirus.
In February 2020, a team at Westlake University utilized cryo-EM (electron microscopy) to analyze the full-length structure of ACE2, the receptor of SARS-CoV-2, and the complex structure of the full-length ACE2 with the receptor-binding domain of SARS-CoV-2 spike protein and revealing the first moment the virus hijacked human cells. The work is the world’s first analysis of the full-length structure of ACE2. The research paper, Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2, has been published as a cover article on Science and Dr. Renhong Yan is the first author.
During Renhong’s Ph.D study, he mainly focused on studying the structure and function of the amino acid transporter complex, the LAT1-4F2hc, which is responsible for transporting large neutral amino acid and hormone precursors. He successfully analyzed the structure of the complex using cryo-EM and proved that the heavy chain protein 4F2hc is necessary for LAT1 to play its transport activity. It was the first time that scientists determined the high-resolution structure of integrated membrane proteins under 100 kDa visible region without symmetry by cryo-EM technology, which plays an important structural foundation for the development of anticancer drugs.
At the beginning of 2020, the outbreak of SARS-CoV-2 soon led to a global pandemic. Renhong quickly turned his research objective to figure out the interaction mechanism between ACE2 and S protein of SARS-CoV-2. During the Chinese Spring Festival, Renhong gave up his family time, strived for breakthroughs in research, and used cryo-EM to analyze the high-resolution structure and interaction mechanism of the SARS-CoV-2 receptor binding domain with the full-length ACE2.
Renhong revealed that his next research goal can be divided into two categories: the first is to study the amino acid transporter B⁰AT1 and the second is to continue to investigate the molecular mechanism of the S protein on the surface of SARS-CoV-2 to find effective drugs to inhibit virus infection.