Investigating Early Aggregation Processes using Mass Spectrometry
- Event time: 1:00pm
- Event date: 8th March 2010
- Speaker: Harriet Cole (Formerly School of Physics & Astronomy, University of Edinburgh)
- Location: Room 2511, James Clerk Maxwell Building (JCMB) James Clerk Maxwell Building Peter Guthrie Tait Road Edinburgh EH9 3FD GB
One of the most common errors to occur in the protein folding process is the formation of fibrillar aggregates, known as amyloid fibrils. Over forty human diseases are characterised by the deposition amyloid fibrils and investigations into the aggregation processes are likely to be valuable in fighting these diseases. To this end the early stage aggregation processes of two systems have been studied. The first is the endecapeptide TTR (105-115) which has been widely utilised as a model system for investigating amyloid formation due to its convenient size. The second is bovine insulin; a larger and more complex protein whose aggregation in vitro has great ramifications in terms of diabetes treatments.
In the current study oligomers formed early in the process of fibril assembly are observed by mass spectrometry (MS) on a QToF2 platform. MS is the only technique which allows the early species to be characterised as it can identify species and different oligomeric orders by mass to charge ratio and show the peptide abundance and its aggregation propensity. The gas phase structural arrangements of the oligomers were measured by ion mobility mass spectrometry (IMMS). IMMS is used to examine the change in the population of oligomers in the aggregating solution. The distribution of oligomers found via nano-electrospray ionisation (nESI) MS and their collision cross sections are reported and the change in the population of oligomers and in their collision cross-sections as a function of time compared. Collision cross sections have finally been compared with molecular dynamics simulations to ascertain structural details about the oligomers.
This is a weekly series of informal talks given primarily by members of the soft condensed matter and statistical mechanics groups, but is also open to members of other groups and external visitors. The aim of the series is to promote discussion and learning of various topics at a level suitable to the broad background of the group. Everyone is welcome to attend..