KHARE, Shashank; VILLALBA, Miryam; CANUL-TEC, Juan; CAJIAO, Arantza; KUMAR, Anand; BACKOVIC, Marija; REY, Felix; PARDON, Els; STEYAERT, Jan; PEREZ, Camilo; REYES, Nicolas

doi:10.1038/s41594-024-01295-6

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KHARE, Shashank
Microbiologie Fondamentale et Pathogénicité [MFP]

VILLALBA, Miryam
Microbiologie Fondamentale et Pathogénicité [MFP]

CANUL-TEC, Juan
Microbiologie Fondamentale et Pathogénicité [MFP]

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Article de revue

Ce document a été publié dans

Nature Structural and Molecular Biology. 2024-09, vol. 31, n° 9, p. 1368 - 1376

Résumé en anglais

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.< Réduire

Mots clés en anglais

Electron microscopy

Membrane proteins

Structural biology

Viral membrane fusion

URI

https://oskar-bordeaux.fr/handle/20.500.12278/204994

DOI

http://dx.doi.org/10.1038/s41594-024-01295-6

Projet Européen

Transport and Receptor Mechanisms of Human Solute Carriers

Project ANR

Integrative Biology of Emerging Infectious Diseases

Unités de recherche

MFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234