Authors:

Hugo Ortiz-Garcia

Date Created:

Not specified

Course Title:

Professor:

Not specified

About Paper:

The filamentation induced by cAMP (Fic) adenylyltransferases have a vital role in cellular signaling via a unique post-transitional modification called AMPylation. The variant HYPE (Huntingtin yeast interacting protein E), only found in humans, has an important role in the adenylylation of the endoplasmic reticulum (ER) molecular chaperone BiP that regulates ER homeostasis by targeting misfolded proteins and managing ER stress. The focus of this study is Brucella abortus, an intracellular pathogen that can induce the unfolded protein response (UPR) by releasing toxins through its type 4 secretion system that manipulate cellular functions.This microorganism causes human brucellosis which is a serious zoonotic disease that represents a risk of abortion in pregnant women and poses a risk to animal health. Infected animals may experience reduced fertility resulting in significant economic and agricultural impacts. The aim of this research is to understand VceC, an effector of B. abortus, and its proline-rich (PR) domain; previous studies have demonstrated their correlation with UPR induction. We aim to isolate and purify VceC's PR domain in order to determine its structure and study its interactions with HYPE and BiP. Despite previous unsuccessful attempts using computational methods like AlphaFold2, our aim is to solve the structure of the purified PR domain and determine its role in UPR on mammalian cells. Using modern biochemical techniques we can comprehensively understand VceC's contribution to host ER stress response induction and determine the potential cytotoxicity of its PR domain.

Source:

Purdue University / 2023

Topics:

No topics listed

Co-authors:

Hugo Ortiz-Garcia