Biochemistry Seminar: David Eliezer
Wed, Dec 11
12:00 PM — 1:00 PM
Marshak160 Convent Avenue
David Eliezer, "Disorder to Order Transitions inDavid Eliezer, Assoc Prof., Depts of Biochemistry and Neuroscience, Weill Cornell Medical College, will give a talk titled, "Disorder to Order Transitions in Neuro-transmission and -degeneration."
Neuro-transmission and -degeneration"
ABSTRACT: This talk will focus on the role of three different disordered proteins in processes linked to neurodegeneration and neurotransmission and will seek to illustrate the power of structural biology in formulating models for the function and dysfunction of such proteins. The protein alpha-synuclein is genetically and histopathologically associated with familial and sporadic Parkinson's disease. Although considered to belong to the category of intrinsically disordered proteins for well over a decade, recent reports have suggested that synuclein may actually exist predominantly in a native, well-structured, tetrameric form. Experiments using in-cell NMR, which bypass potential structural perturbations caused by purification protocols, conclusively demonstrate that recombinant synuclein is in fact highly disordered and monomeric. In the presence of membranes, however, the protein undergoes a coil-to-helix transition to adopt several highly helical conformations, which are proposed to mediate both its normal function and its membrane-induced aggregation into amyloid fibrils. The effects of N-terminal acetylation, a common eukaryotic protein modification, on synuclein structure and membrane interactions prove interesting to examine. Recently, synuclein has been proposed to modulate synaptic vesicle exocytosis via either direct or indirect interactions with SNARE proteins and complexes. Interestingly, one of the few proteins that responds to changes in syncline levels in cells is the protein complexin, which also regulates SNARE-mediated vesicle fusion. Like synuclein, the C-terminal domain of complexin is intrinsically disordered, yet can be demonstrated to interact with membranes in a manner that is required for proper complexion function. Tau is a microtubule-binding protein that forms filamentous aggregates linked to Alzheimer’s disease and other dementias but little is known about its microtubule bound state. Tau also interacts with anionic lipids and detergents in ways that may recapitulate important aspects of both its microtubule interactions and its pathological aggregation.