Structural and functional characterizations of mitochondrial calcium uniporter
Abstract/Contents
- Abstract
- In this thesis, I mainly worked on the structural and functional characterization of a mitochondrial calcium channel named MCU. Mitochondrial calcium plays critical roles in a wide range of fundamental cellular processes, including controlling the rate of ATP production, regulating the initiation of cell death and shaping cytosolic calcium signaling. Since fifty years ago when it was first demonstrated that fully energized mitochondria can rapidly load up calcium ions (Ca2+), the machinery behind this process has been extensively explored. This uptake is mediated by a highly selective calcium channel called the mitochondrial calcium uniporter (MCU), which resides on the inner mitochondrial membrane. The molecular identity of the uniporter was only uncovered relatively recently. MCU bears no discernable sequence similarity to other known channels and represents a new class in ion channels with its unique selectivity and conductance properties. In this thesis, I used both X-ray crystallography and single-particle cryo-electron microscopy to determine the structures of MCU from two species containing all domains, and I established rapid and efficient functional characterization platforms in cells and in liposomes. Unexpectedly, the stoichiometry, overall architecture, and local structural details of the new structures differed markedly from the NMR cMCU structure. The physiological relevance of those structures was corroborated by the observation of a consistent architecture across species and chemical environments, and by the systematical functional assays. Structural and functional characterizations provided insights into Ca2+ coordination, selectivity, and permeation, establishing a framework for understanding the mechanism of MCU function.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2018; ©2018 |
| Publication date | 2018; 2018 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Fan, Chao |
|---|---|
| Degree supervisor | Feng, Liang, 1976- |
| Thesis advisor | Feng, Liang, 1976- |
| Thesis advisor | Kobilka, Brian K |
| Thesis advisor | Lewis, Richard |
| Thesis advisor | Maduke, Merritt C, 1966- |
| Degree committee member | Kobilka, Brian K |
| Degree committee member | Lewis, Richard |
| Degree committee member | Maduke, Merritt C, 1966- |
| Associated with | Stanford University, Department of Molecular and Cellular Physiology. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Chao Fan. |
|---|---|
| Note | Submitted to the Department of Molecular and Cellular Physiology. |
| Thesis | Thesis Ph.D. Stanford University 2018. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2018 by Chao Fan
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