Abstract
The HML2 (HERV-K) group constitutes the most recently acquired family of human endogenous retroviruses, with many proviruses less than one million years old. Many maintain intact open reading frames and provirus expression together with HML2 particle formation are observed in early stage human embryo development and are associated with pluripotency as well as inflammatory disease, cancers and HIV-1 infection. Here, we reconstruct the core structural protein (CA) of an HML2 retrovirus, assemble particles in vitro and employ single particle cryogenic electron microscopy (cryo-EM) to determine structures of four classes of CA Fullerene shell assemblies. These icosahedral and capsular assemblies reveal at high-resolution the molecular interactions that allow CA to form both pentamers and hexamers and show how invariant pentamers and structurally plastic hexamers associate to form the unique polyhedral structures found in retroviral cores.
Highlights
The HML2 (HERV-K) group constitutes the most recently acquired family of human endogenous retroviruses, with many proviruses less than one million years old
Our studies of HML2 CArec show that an ERV retains the ability to form capsid assemblies using the same architecture as exogenous viruses
The full diversity of interactions we observe in our structures reveals (1) plasticity of packing at the NTD–NTD interfaces, (2) alternative geometry and bonding configurations at the NTD–CTD interfaces and (3) the quantisation of the CTD–CTD association parameters
Summary
The HML2 (HERV-K) group constitutes the most recently acquired family of human endogenous retroviruses, with many proviruses less than one million years old. We reconstruct the core structural protein (CA) of an HML2 retrovirus, assemble particles in vitro and employ single particle cryogenic electron microscopy (cryo-EM) to determine structures of four classes of CA Fullerene shell assemblies These icosahedral and capsular assemblies reveal at highresolution the molecular interactions that allow CA to form both pentamers and hexamers and show how invariant pentamers and structurally plastic hexamers associate to form the unique polyhedral structures found in retroviral cores. Several members of the HML2 group of ERVs have proviruses less than one million years old[3,4,5,6] with intact ORFs7 and HML2 particle formation is observed in early-stage human embryo development[8] and is associated with pluripotency[9], as well as inflammatory disease[10,11,12], cancers[13,14,15,16] and HIV-1 infection[17,18,19]. Analysis of the shell structures reveals the intra- and inter-molecular interactions that drives CA assembly into pentamers and hexamers and their association into shells that encapsidate the retroviral genome
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