Explore a groundbreaking lecture on structural biology that revolutionized the field by studying proteins in the vapor phase. Delve into Carol Robinson's innovative research, which provides a new perspective on protein interactions and their behavior beyond solid and solution phases. Learn how this unconventional approach has proven invaluable in understanding dynamic interactions between proteins, lipids, and drugs. Discover the journey from early mass spectrometry techniques to cutting-edge applications in studying membrane proteins, drug resistance mechanisms, and the impact on human health. Gain insights into the scientific goals, methodologies, and breakthroughs that have shaped this new phase of structural biology, including the analysis of complex protein structures, evolutionary assembly pathways, and the role of lipids in protein stability.
Overview
Syllabus
Intro
Count Rumford one of the founding members of the Royal Institution
J.J. Thomson unveiled the discovery of the electron
First mass spectrometers
Mass spectrum of aspirin
Mass Spectrum of Melanocyte Stimulating Hormone
Nobel prize for chemistry 2002
Electrospray - without unfolding
Folding in the presence of molecular chaperones
A new phase for structural biology?
Proteins with many different conformations
The passage of complexes through the mass spectrometer
Scientific goals and questions
Unraveling polydispersity - the alpha crystallins
Disassembly predicts evolutionary assembly pathways
Mass spectrometry to identify the building blocks within complexes
Micelles protect membrane complexes and lipid binding remains intact
From micelles to membrane proteins in the gas phase
ATP Synthase - 95:1 DDM: protein
Mass spectrum of intact ATPase from Thermus thermophilus
Mass spectral assignment strategy - Massign
New ways to study how small molecules stabilise membrane proteins
Monitoring unfolding of AqpZ as a function of POPG binding
P-glycoprotein - an ABC transporter and drug efflux pump
Looking for a small difference
Mechanisms of drug resistance
Zinc binding to a human metalloprotease ZMPSTE24
Progeria is a common side effect of anti- HIV drugs
Processing of lamin A peptides is inhibited by drug binding
Sugar transporter semiSWEET - remodeling the lipid bilayer
From Neon to rotary motors to flipping lipids and drugs
Taught by
The Royal Institution
