Deep time structural evolution of retroviral and filoviral surface envelope proteins

The retroviral surface envelope protein subunit (SU) mediates receptor binding and triggers membrane fusion by the transmembrane subunit (TM). SU evolves rapidly under strong selective conditions, resulting in seemingly unrelated SU structures in highly divergent retroviruses. Structural modeling of the SU of several retroviruses and related endogenous retroviral elements with AlphaFold identifies a TM-proximal SU β-sandwich structure that has been conserved in the orthoretroviruses for at least 110 million years. The SU of orthoretroviruses diversified by differential expansion of the β-sandwich core to form domains involved in virus-host interactions. The β-sandwich domain is also conserved in the SU equivalent GP1 of Ebola virus although with a significantly different orientation in the trimeric envelope protein structure. The unified structural view of orthoretroviral SU and filoviral GP1 identifies an ancient, structurally conserved and evolvable domain underlying the structural diversity of orthoretroviral SU and filoviral GP1.