info:eu-repo/semantics/article
Short linear motif candidates in the cell entry system used by SARS-CoV-2 and their potential therapeutic implications
Fecha
2021-01-12Registro en:
Mészáros, Bálint; Sámano Sánchez, Hugo; Alvarado Valverde, Jesús; Čalyševa, Jelena; Martinez Perez, Elizabeth; et al.; Short linear motif candidates in the cell entry system used by SARS-CoV-2 and their potential therapeutic implications; American Association for the Advancement of Science; Science Signaling; 14; 665; 12-1-2021; 1-26
1945-0877
1937-9145
CONICET Digital
CONICET
Autor
Mészáros, Bálint
Sámano Sánchez, Hugo
Alvarado Valverde, Jesús
Čalyševa, Jelena
Martinez Perez, Elizabeth
Alves, Renato
Shields, Denis C.
Kumar, Manjeet
Rippmann, Friedrich
Chemes, Lucia Beatriz
Gibson, Toby James
Resumen
The first reported receptor for SARS-CoV-2 on host cells was the angiotensin-converting enzyme 2 (ACE2). However, the viral spike protein also has an RGD motif, suggesting that cell surface integrins may be co-receptors. We examined the sequences of ACE2 and integrins with the Eukaryotic Linear Motif (ELM) resource and identified candidate short linear motifs (SLiMs) in their short, unstructured, cytosolic tails with potential roles in endocytosis, membrane dynamics, autophagy, cytoskeleton, and cell signaling. These SLiM candidates are highly conserved in vertebrates and may interact with the μ2 subunit of the endocytosis-associated AP2 adaptor complex, as well as with various protein domains (namely, I-BAR, LC3, PDZ, PTB, and SH2) found in human signaling and regulatory proteins. Several motifs overlap in the tail sequences, suggesting that they may act as molecular switches, such as in response to tyrosine phosphorylation status. Candidate LC3-interacting region (LIR) motifs are present in the tails of integrin β3 and ACE2, suggesting that these proteins could directly recruit autophagy components. Our findings identify several molecular links and testable hypotheses that could uncover mechanisms of SARS-CoV-2 attachment, entry, and replication against which it may be possible to develop host-directed therapies that dampen viral infection and disease progression. Several of these SLiMs have now been validated to mediate the predicted peptide interactions.