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Structure and Function of Macromolecular Complexes by Multidimensional High-Field Magic-Angle Spinning NMR


EMSL Project ID
44750

Abstract

We aim to explore the limits of performance for high-field (900 MHz) magic-angle spinning NMR studies of non-crystalline solid proteins, in order to solve high-resolution structures of macromolecular complexes, including membrane proteins and fibrils. Proteins linked to disease phenotypes, including neurodegenerative diseases and circulatory disorders, are often found in membrane-associated or aggregated states, whose physical properties severely impede examination by x-ray crystallography or solution NMR. With such challenging sample conditions, atomic-resolution insight into molecular structure by solid-state NMR is a prime example of discovery and technical innovation through experimental science. We envision that results with the improved instrumental power of resources uniquely available at EMSL will facilitate an improved structural and functional understanding of membrane proteins, an important class of proteins for drug discovery and bioenergetics, as well as fibrillar aggregates associated with Parkinson's disease, prion proteins and complexes of enzymes that accelerate blood coagulation in a phospholipid-dependent manner.

Project Details

Project type
Large-Scale EMSL Research
Start Date
2011-10-01
End Date
2012-09-30
Status
Closed

Team

Principal Investigator

Chad Rienstra
Institution
University of Illinois at Urbana-Champaign

Team Members

Joseph Courtney
Institution
University of Illinois at Urbana-Champaign

Ming Tang
Institution
University of Illinois at Urbana-Champaign

Eric Watt
Institution
University of Illinois at Urbana-Champaign

Kristin Nuzzio
Institution
University of Illinois at Urbana-Champaign

Christopher Jaroniec
Institution
The Ohio State University

Gemma Comellas Canal
Institution
University of Illinois at Urbana-Champaign

Lindsay Sperling
Institution
University of Illinois at Urbana-Champaign

Andrew Nieuwkoop
Institution
University of Illinois at Urbana-Champaign

Related Publications

Comellas Canal G, LR Lemkau, AJ Nieuwkoop, KD Kloepper, DT Ladror, R Ebisu, WS Woods, AS Lipton, JM George, and CM Rienstra. 2011. "Structured Regions of Alpha-synuclein Fibrils Include the Early Onset Parkinson's Disease Mutation Sites." Journal of Molecular Biology 411(4):881-895. doi:10.1016/j.jmb.2011.06.026