Life Sciences & Biotechnology
Title : | Deciphering the molecular mimicry by bacterial effector Lpg2455/GobX, a U-Box E3 ubiquitin ligase manifesting host immune evasion during Legionella infection. |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Molecular Biology, Immunology |
Principal Investigator : | Dr. Pooja Kumari, Amity University, Noida, Uttar pradesh Jharkhand |
Timeline Start Year : | 2023 |
Timeline End Year : | 2025 |
Contact info : | kashyappooja1902@gmail.com |
Details
Executive Summary : | Post-translational modifications (PTM) play a crucial role in cellular homeostasis, with ubiquitination being a unique PTM exclusive to eukaryotic systems. Pathogenic bacteria, such as Legionella pneumophila, have exploited this process to invade alveolar macrophages and evade host immune responses. Legionella delivers around 300 effector proteins, which help establish a Legionella containing vacuole, supporting Legionnaires pneumonia. Around 20 of these proteins exploit the host ubiquitin machinery to establish infection. One critical effector protein characterized is Lpg2455, which exhibits auto-ubiquitination activity in the absence of substrates and the presence of human E2 ubiquitin-conjugating enzymes. However, it lacks sequence homology to other proteins but has remote secondary structure homology to U-box E3 ligase. The structure of GobX, a Legionella GobX function, is currently unavailable, and its molecular mechanism is poorly understood. The proposal aims to characterize the molecular basis of GobX substrate recognition and delineate their structure-function relationship. The sequence diversity of GobX and their subcellular localization suggest they may target several host proteins. The study aims to identify the host substrates ubiquitinated by GobX, determine the high-resolution crystal structures of GobX, and biochemically characterize its interactions to discern its functional mechanism. These studies will be vital for understanding the functional mechanism of GobX and designing inhibitors. |
Total Budget (INR): | 26,81,523 |
Organizations involved