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 (TM) subunit. SU
evolves rapidly under strong selective conditions, resulting in seemingly
unrelated SU structures in highly divergent retroviruses. Structural
modeling of the SUs of several retroviruses and related endogenous
retroviral elements with AlphaFold 2 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 the
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 relative
to the β-sandwich of human immunodeficiency virus type 1 gp120, with
significant evidence for divergent rather than convergent evolution. 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.