H2020Индивидуална стипендия2017–2019

HBVssNMR · Investigating the structural role of the Hepatitis B virus core protein C-terminal domain in assembly and maturation using solid-state NMR

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2017-06-01 → 2019-05-31
Финансиране от ЕС: 143 603 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Структурата и движението на C-терминалния домейн на протеина в капсулата на вируса на хепатит B се анализират чрез ядромагнитен резонанс. Това помага да се разбере как вирусът опакова генетичния си материал и се придвижва в клетката.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Investigating the structural role of the Hepatitis B virus core proteinC-terminal domain in assembly and maturation using solid-stateNMR

Despite the existence of an efficient vaccine, the hepatitis B virus (HBV) affects about 240 million people in the world who remain chronically infected. The HBV viral particle (virion) is composed of a nucleocapsid that is surrounded by lipids and envelope proteins. The capsid is ~30 nm in diameter and is made from 120 copies of the core protein (Cp) dimers. Cp contains an N-terminal domain (NTD) which is responsible for the capsid assembly, and a C-terminal domain (CTD), which interacts with the viral RNA called pregenomic RNA (pgRNA). The CTD undergoes dynamic phosphorylation and dephosphorylation events that regulate its function. Its conformation seems therefore to be central in several critical steps along the viral life cycle, including the specific encapsidation of pgRNA and the intracellular trafficking to the nucleus. However, it remains very challenging to observe the CTD conformation by X-ray diffraction, as it is highly flexible. Even high-resolution cryo-EM studies do not reveal sufficiently detailed information for the CTD. Instead, NMR is a powerful tool to study conformational and dynamical aspects of biomolecules, especially flexible domains like the CTD. The global aim of the project was to use solid-state NMR to study the HBV capsids, in particular to reveal structural and dynamic features of its C-terminal domain.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

We will seek in this project to reveal structural and dynamic features of the C-terminal domain (CTD) of the Hepatitis B virus (HBV) core protein which encapsidates the viral genome. Each year, over 750,000 deaths are due to serious liver diseases caused by chronic HBV infection. Hepatitis B is, despite the availability of a vaccine, still a major health problem. The HBV virus particle is composed of an outer lipid-protein envelope and a core protein of 20 kDa that self-assembles into icosahedral nucleocapsids. The nucleocapsid encloses the pregenomic RNA (pgRNA) that is then reverse-transcribed into DNA by the viral polymerase (Pol). During pgRNA encapsidation, the CTD is thought to interact with the RNA. Despite the essential role played by the CTD in the regulation of the viral life cycle through various conformational states and phosphorylation patterns, it escapes today to classical structural biology approaches due to its dynamic nature. We will use solid-state NMR to bring new insights into the precise conformation and localization of the CTD along various steps of the viral life cycle. Sample preparation protocols of the core protein have recently been established by the applicant in the host laboratory using bacterial expression systems. The first NMR spectra of the nucleocapsid look highly promising. Further experiments will be recorded to assign the resonances and identify the CTD signals. Different phosphorylation states and binding partners, as the pgRNA, will be explored. Finally, paramagnetic tags will be used to obtain information about the positioning of the CTD. Our work shall contribute to expand the present molecular description of the HBV life cycle to include the role of the CTD. Our results will help to understand, and ultimately to target, its central role in HBV infection.

Оригинален текст от CORDIS (на английски).

Участници

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisКоординаторФранция