Native Mass spectrometry as a novel drug discovery method for membrane proteins

Tue23  Feb12:00pm(20 mins)
Where:
Conference Room 1
Speaker:
 Jason Yen

Abstract

Native mass spectrometry (MS) can be used to characterize proteins without disrupting the non-covalent interactions that maintain their structural integrity as well as their interactions with ligands. Whilst this methodology has been applied to soluble proteins widely, its application to membrane proteins has been challenging due to the presence of detergent micelles. Recent technical advances in membrane protein biochemistry as well as instruments has led to the development of membrane protein specific protocols. Utilizing native MS on membrane proteins such as GPCRs represents a novel and highly differentiated technique to interrogate the biology of these important class of proteins. Specifically, for GPCRs that we have demonstrated that native MS allows identification of novel endogenous ligands that co-purify with the receptor as well as hits from a complex library of synthetic compounds. Moreover, through analysis of the interaction of the receptor with the downstream signalling molecules (e.g. G-proteins), the pharmacology of ligands can be observed directly. Given the high resolution and high content nature of the native MS approach, these data demonstrate that application of native MS to GPCRs represents an exciting platform that can be used to screen complex libraries more importantly characterize the functional consequences of compound binding in a biophysical technique.
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