Structure of the Core Postfusion Porcine Endogenous Retrovirus Fusion Protein

Area of Science:

• Structural Biology
• Virology
• Molecular Evolution

Background:

• Endogenous retroviruses (ERVs) possess functional elements, including envelope glycoproteins involved in mammalian physiology.
• Porcine endogenous retroviruses (PERVs) are understudied, with their envelope glycoproteins poorly characterized, despite potential implications for xenotransplantation.
• The PERV envelope glycoprotein is a candidate for swine syncytin, potentially playing a role in placental development.

Purpose of the Study:

• To determine the postfusion crystal structure of the PERV core fusion ectodomain.
• To analyze the structural and evolutionary relationships of PERV fusogens with other class I viral fusion proteins.
• To infer the membrane fusion mechanisms of endogenous retroviral fusogens.

Main Methods:

• Determination of the postfusion crystal structure of the PERV core fusion ectodomain.
• Biophysical experiments to assess the thermodynamic stability of the PERV fusion protein.
• Sequence conservation analysis and structural alignment of class I viral fusogens.

Main Results:

• The PERV fusion protein structure exhibits a conserved class I viral fusion protein six-helix bundle.
• The protein's secondary structure stability is consistent at both physiological and acidic pH.
• Structural and phylogenetic analyses reveal conserved features among retroviral fusogens and distinct evolutionary lineages correlating with cell entry mechanisms.

Conclusions:

• The PERV fusion protein shares structural similarities with exogenous retroviral fusogens, suggesting conserved mechanisms for membrane fusion.
• Structural dendrograms can be utilized to infer fusion mechanisms of newly discovered class I viral fusogens.
• This study provides mechanistic insights into ancient retroviral elements captured in eukaryotic genomes.