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You searched for +publisher:"University of North Carolina" +contributor:("Grabon, Agnieszka"). One record found.

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University of North Carolina

1. Grabon, Agnieszka. Atomistic and Cellular Analysis of Start Phosphatidylinositol Transfer Proteins in the Context of the Phospholipid Extraction Mechanism and Phosphoinositide Signaling in the Parasite Toxoplasma.

Degree: Cell Biology and Physiology, 2016, University of North Carolina

Phosphatidylinositol transfer proteins (PITPs) are essential regulators of the interface between phosphoinositide (PIP) signaling and membrane trafficking in eukaryotic cells. Genetic derangement of PITPs in multicellular organisms results in pathologies such as neurodegeneration, metabolic diseases, and vision and neurosensory defects. How PITPs sense multiple metabolic inputs to specify a membrane signaling event is key to our understanding of these pathologies and of PIP networks in general. To that end, we describe a novel multi-domain PITP of the START structural family: PITP Multidomain Protein (PIMP) is encoded by the eukaryotic parasite Toxoplasma, and associated with specialized parasite organelles called dense granules. Dense granules are secretory organelles that traffic Toxoplasma proteins during parasite infection of the mammalian host. PIMP links a PITP domain to an oxysterol binding protein (OSBP) domain. PITP and OSBP orthologs in other eukaryotes are expressed as separate proteins known to antagonize each other in specific PIP signaling pathways. We report that PIMP is a bona fide PITP in vivo and in vitro, and its binding and extraction of phosphatidylinositol (PtdIns) from membranes is required for this function. Furthermore, PIMP binds phosphatidylcholine as a counter-ligand to PtdIns, and senses specific higher order PIPs, PtdIns4P and PtdIns(4,5)P2 through a conserved plekstrin homology (PH) domain. We describe how Toxoplasma codes its secretory system with unique PtdIns4P pools, and define PIMP as a sensor of PIP pools on dense granules. Thus PIMP is a dense granule protein that represents a novel platform for the integration of multiple metabolic inputs with PtdIns4P signaling. The mechanism by which the PIMP PITP domain, or indeed any START PITP, extracts phospholipids from bilayers is unknown. We performed molecular dynamics simulations using the mammalian PITPĪ± as a START PITP model. We report atomistic detail of the trajectory of phospholipids into the START PITP binding pocket. Overall, this work analyzes START PITP function on the atomistic and cellular levels, and offers possible explanations for how these proteins organize specific PIP signaling events. Advisors/Committee Members: Grabon, Agnieszka, Bankaitis, Vytas A., Burridge, Keith, Hammond, Scott, Major, Ben, Weiss, Ellen.

Subjects/Keywords: School of Medicine; Department of Cell Biology and Physiology

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APA (6th Edition):

Grabon, A. (2016). Atomistic and Cellular Analysis of Start Phosphatidylinositol Transfer Proteins in the Context of the Phospholipid Extraction Mechanism and Phosphoinositide Signaling in the Parasite Toxoplasma. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:686007f0-702c-405a-9545-7dafd11bd8fa

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Grabon, Agnieszka. “Atomistic and Cellular Analysis of Start Phosphatidylinositol Transfer Proteins in the Context of the Phospholipid Extraction Mechanism and Phosphoinositide Signaling in the Parasite Toxoplasma.” 2016. Thesis, University of North Carolina. Accessed October 28, 2020. https://cdr.lib.unc.edu/record/uuid:686007f0-702c-405a-9545-7dafd11bd8fa.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Grabon, Agnieszka. “Atomistic and Cellular Analysis of Start Phosphatidylinositol Transfer Proteins in the Context of the Phospholipid Extraction Mechanism and Phosphoinositide Signaling in the Parasite Toxoplasma.” 2016. Web. 28 Oct 2020.

Vancouver:

Grabon A. Atomistic and Cellular Analysis of Start Phosphatidylinositol Transfer Proteins in the Context of the Phospholipid Extraction Mechanism and Phosphoinositide Signaling in the Parasite Toxoplasma. [Internet] [Thesis]. University of North Carolina; 2016. [cited 2020 Oct 28]. Available from: https://cdr.lib.unc.edu/record/uuid:686007f0-702c-405a-9545-7dafd11bd8fa.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Grabon A. Atomistic and Cellular Analysis of Start Phosphatidylinositol Transfer Proteins in the Context of the Phospholipid Extraction Mechanism and Phosphoinositide Signaling in the Parasite Toxoplasma. [Thesis]. University of North Carolina; 2016. Available from: https://cdr.lib.unc.edu/record/uuid:686007f0-702c-405a-9545-7dafd11bd8fa

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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