Sequence requirements of the FFAT-like motif for specific binding to VAP-A are revealed by NMR

[摘要] The endoplasmic reticulum transmembrane protein vesicle-associated membrane protein-associated protein (VAP) plays a central role in the formation and function of membrane contact sites (MCS) through its interactions with proteins. The major sperm protein (MSP) domain of VAP binds to a variety of sequences which are referred to as FFAT-like motifs. In this study, we investigated the interactions of eight peptides containing FFAT-like motifs with the VAP-A MSP domain (VAP-A MSP ) by solution NMR. Six of eight peptides are specifically bound to VAP-A. Furthermore, we found that the RNA-dependent RNA polymerase of severe acute respiratory syndrome coronavirus 2 has an FFAT-like motif which specifically binds to VAP-A MSP as well as other FFAT-like motifs. Our results will contribute to the discovery of new VAP interactors.

[关键词] FFAT motif;FFAT-like motif;protein–protein interaction;SARS-CoV-2;solution NMR;VAMP-associated protein