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Published on: February 7, 2019
Sequence requirements of the FFAT-like motif for specific binding to VAP-A are revealed by NMR
Kyoko Furuita1, Marina Hiraoka2, Kentaro Hanada3
1Institute for Protein Research, Osaka University, Suita, Japan.
Abstract:
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-AMSP ) 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-AMSP as well as other FFAT-like motifs. Our results will contribute to the discovery of new VAP interactors.
Insights
Vesicle-associated membrane protein-associated protein (VAP) interacts with FFAT-like motifs. This study found six peptides and SARS-CoV-2 RNA polymerase bind to VAP-A, identifying new VAP interactors.
Area of Science:
- Cell biology
- Protein-protein interactions
- Structural biology
Background:
- Vesicle-associated membrane protein-associated protein (VAP) is crucial for membrane contact site (MCS) formation.
- VAP utilizes its major sperm protein (MSP) domain to bind FFAT-like motifs on interacting proteins.
Purpose of the Study:
- To investigate the binding interactions between VAP-A's MSP domain and various FFAT-like motifs.
- To identify potential new VAP interactors, including viral proteins.
Main Methods:
- Solution Nuclear Magnetic Resonance (NMR) spectroscopy was employed.
- Eight synthetic peptides containing FFAT-like motifs were tested for binding to VAP-A's MSP domain.
Main Results:
- Six out of eight tested peptides specifically bound to the VAP-A MSP domain.
- The RNA-dependent RNA polymerase of SARS-CoV-2 was identified to possess a functional FFAT-like motif that binds to VAP-A.
Conclusions:
- The study elucidates specific binding interactions between VAP-A and FFAT-like motifs.
- Findings suggest VAP-A as a potential host factor for SARS-CoV-2 and open avenues for discovering novel VAP-interacting proteins.
