Life Sciences Commons^™

Uncovering The Structural Basis For Mitochondrial Calcium Uniporter Dominant Negative Beta Subunit (Mcub) Function, Megan L. Noble

Electronic Thesis and Dissertation Repository

Mitochondrial calcium (Ca²⁺) uptake is regulated by the mitochondrial Ca²⁺ uniporter (MCU), a tetrameric channel that is regulated by interactions with several accessory proteins, including MCU dominant negative beta subunit (MCUb). MCUb inhibits Ca²⁺ uptake by assembling into the MCU complex and is incapable of forming a functional Ca²⁺ channel. The MCU amino (N)-terminal domain plays an essential role in controlling MCU structure and function and contains cation binding sites that, when bound by Ca²⁺ and magnesium (Mg²⁺), cause decreased MCU assembly and reduced mitochondrial Ca²⁺ uptake. MCU and MCUb contain …

Structure And Function Of Stomatin-Like Protein 2, Safee Mian

Electronic Thesis and Dissertation Repository

Stomatin-like protein 2 (SLP-2), a member of the SPFH superfamily, is a mitochondrial inner membrane protein required for optimal mitochondrial respiration. SLP-2 binds to the important mitochondrial phospholipid cardiolipin (CL) and has been proposed to mediate formation of CL-enriched microdomains that would foster respiratory chain supercomplex (RCS) formation and stability. However, little is known about how SLP-2 structure facilitates its cellular function. The goal of this thesis was to elucidate if and how SLP-2 oligomerizes and by what means does it bind CL.

Biophysical analysis of the expressed SLP-2 SPFH domain, either with or without flanking residues, indicates it to …

The Mitochondrial Calcium Uniporter Regulator 1 (Mcur1) Matrix Domain Is A Self-Associated Multimer Sensitive To Divalent Cations, Naveed Siddiqui

Electronic Thesis and Dissertation Repository

Mitochondria are primarily appreciated for the generation of adenosine triphosphate (ATP), a chemical store of energy required by all cells. These organelles, however, also play key roles in apoptosis, autophagy and shaping cytosolic calcium (Ca²⁺) signaling via Ca²⁺ uptake into the mitochondrial matrix. This Ca²⁺ uptake is mediated chiefly via the mitochondrial Ca²⁺ uniporter (MCU), an inner mitochondrial membrane protein that oligomerizes to form a Ca²⁺ selective pore. MCU is regulated by several protein binding partners, including the recently identified MCU regulator-1 (MCUR1). MCUR1 stabilizes a higher order MCU heterocomplex through interactions with MCU …

Interaction Of Seca With Unfolded Polypeptides, Aliakbar Khalili Yazdi

Electronic Thesis and Dissertation Repository

The evolutionarily well-conserved SecA is essential for bacterial post-translational translocation. SecA uses the energy of ATP to drive preproteins through the membrane pore. The functional oligomeric state of SecA and the molecular basis for recognition of unfolded polypeptides by SecA are major unresolved questions that must be addressed to understand preprotein targeting and the molecular mechanics of SecA-mediated translocation. This thesis will address three aspects of these questions. First, the role of unstructured termini in the oligomerization and function of various SecA constructs was elucidated. By re-examining the tetramerization of a truncated SecA construct (SecA-N68), it was shown that the …