SARS-CoV-2 envelope protein and its relationship to the membrane protein

Abstract

The structural proteins located on the SARS-CoV-2 envelope, namely the spike, membrane and envelope protein, play important roles during the entire viral infection cycle. For example, the interaction between the membrane protein and the other structural proteins results in the formation of new virions, while the envelope protein then mediates their secretion. The membrane protein and envelope protein are considered potential drug targets, driving future exploration of their structures and interactions. However, research efforts are complicated as both proteins are membrane-bound and have several functions depending on their tertiary and quaternary structure. Here we review data originating from different sources and explain what is known about the structure and function of these proteins to date.

KEYWORDS:

• SARS-CoV-2
• COVID-19
• envelope protein
• membrane protein
• virion assembly

Acknowledgments

The authors are particularly grateful to Rosemary Wilson for her advice and experience she offered us during the writing process. All figures are courtesy of the Coronavirus Structural Task Force (insidecorona.net), who retains the rights for text and figures. The authors L. Kandler, O. Kippes and M. Edich contributed equally in writing this review and share the first authorship.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung) [grant numbers 05K19WWA and 05K22GU5] and Deutsche Forschungsgemeinschaft [project TH2135/2-1].

Notes on contributors

Luise Kandler

Luise Kandler is a M.Sc. student of Environmental Sciences at the University of Vienna. She did her Bachelor’s degree in Biochemistry at the University of Wuerzburg in 2021 and her bachelor’s thesis with the Thorn Lab with a focus on Structural Biology and Bioinformatics. She joined the Coronavirus Structural Task Force during the first Lockdown in 2020 and was part of the group for one year. At this time, she wrote the first Blog article about the E-protein, but was also involved in other blog articles, literature research, structure descriptions, visualizations and corresponding with media representatives.

Oliver Kippes

Oliver Kippes is a biochemistry B.Sc. student who started working on the nucleocapsid protein as part of the Thorn group. His first work on the protein began with a blog post on their homepage and with entries on the Proteopedia website. As part of the group, he contributed with his knowledge from his studies as well as being an expert in IT. His future goals in the scientific sector are to finish his bachelor and master’s degree and acquire a PhD in molecular biology.

Maximilian Edich

Maximilian Edich studied bioinformatics and genome research in Bielefeld and joined the CSTF as a PhD student in 2021. Previously, his focus was on molecular modelling. Now, he works on the R-factor gap and became an expert for AlphaFold. He already learned what it is like to be part of a young, scientific team as a member of the iGEM contest back in 2017. However, this time revealed also his passion for bioinformatics over working in the lab. Even in his spare time, he enjoys programming. If he isn’t coding his own game or writing a fantasy novel, he’s usually playing pen and paper games or climbing in the bouldering gym.

Sabrina Stäb

Sabrina Stäb is studying biochemistry (M.Sc.) and works as a research assistant for the Thorn Lab and the Coronavirus Structural Task Force. During her bachelor thesis on ‘Crystallization and Structure Solution of High-Quality Structures for MAD Experiments’, she was able to gain a lot of experience in the field of crystallography and now brings this experience to the project. When she doesn’t have to stay at home because of corona, she likes to spend her free time in the bouldering gym or the forest picking mushrooms.

Gianluca Santoni

Gianluca Santoni’s work is focused on the development of methods for synchrotron serial crystallography, from the comparison of datasets for multi-crystal data collection methods to the implementation of new measurement techniques at synchrotron beamlines. He got his PhD in structural biology by studying the structure of acetylcholinesterase in complex with organophosphate nerve agents, applying a mixture of crystallography and computational methods. More recently he has been involved in the data strategies implementation for open science, participating in activities concerning the storage of experimental metadata, the distribution of raw data along with publication according to FAIR principle, and the definition of the Gold standard format for protein diffraction data. His work with the coronavirus structural taskforce has been focused on the implementation of routines to evaluate the quality of both deposited datasets and models.

Andrea Thorn

Andrea Thorn is a specialist for structure solution by crystallography and Cryo-EM, having contributed to programmes like SHELX, ANODE and PHASER in the past. Her group at the University of Hamburg develops AI-based methods in crystallography such as the diffraction diagnostics tool AUSPEX and a neural network for secondary structure annotation of Cryo-EM maps (HARUSPEX). She finds meaningful ways to combine results across techniques and labs to obtain new insights in structural biology and her methods enable other scientists to solve new structures and to answer challenging biological questions. Andrea is very passionate about structural biology and good at bringing people together. She started and leads the Coronavirus Structural Task Force.