8OUJ

Heterotrimeric Complex of Human ASCT2 with Syncytin-1

Summary for 8OUJ

• Entry DOI: 10.2210/pdb8ouj/pdb
• EMDB information: 17194
• Descriptor: Neutral amino acid transporter B(0), Syncytin-1, ALANINE (3 entities in total)
• Functional Keywords: small neutral amino acid transporter, asct2, syncytin-1, receptor binding domain, protein transport
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 226377.81

Authors

Khare, S.,Reyes, N. (deposition date: 2023-04-23, release date: 2024-05-01, Last modification date: 2024-11-13)

Primary citation

Khare, S.,Villalba, M.I.,Canul-Tec, J.C.,Cajiao, A.B.,Kumar, A.,Backovic, M.,Rey, F.A.,Pardon, E.,Steyaert, J.,Perez, C.,Reyes, N.
Receptor-recognition and antiviral mechanisms of retrovirus-derived human proteins.
Nat.Struct.Mol.Biol., 31:1368-1376, 2024

PubMed Abstract: Human syncytin-1 and suppressyn are cellular proteins of retroviral origin involved in cell-cell fusion events to establish the maternal-fetal interface in the placenta. In cell culture, they restrict infections from members of the largest interference group of vertebrate retroviruses, and are regarded as host immunity factors expressed during development. At the core of the syncytin-1 and suppressyn functions are poorly understood mechanisms to recognize a common cellular receptor, the membrane transporter ASCT2. Here, we present cryo-electron microscopy structures of human ASCT2 in complexes with the receptor-binding domains of syncytin-1 and suppressyn. Despite their evolutionary divergence, the two placental proteins occupy similar positions in ASCT2, and are stabilized by the formation of a hybrid β-sheet or 'clamp' with the receptor. Structural predictions of the receptor-binding domains of extant retroviruses indicate overlapping binding interfaces and clamping sites with ASCT2, revealing a competition mechanism between the placental proteins and the retroviruses. Our work uncovers a common ASCT2 recognition mechanism by a large group of endogenous and disease-causing retroviruses, and provides high-resolution views on how placental human proteins exert morphological and immunological functions.

PubMed: 38671230
DOI: 10.1038/s41594-024-01295-6

Experimental method

ELECTRON MICROSCOPY (3.5 Å)