Chemistry: Graduate Lecture Series: (BIO1) Protein Folding, Misfolding and Aggregation (8L)

BIOLOGICAL (BIO)

(BIO1) Protein Folding, Misfolding and Aggregation (8L)

AAN 1. Techniques to study protein structure and stability (Part II Recap) AAN 2. Techniques to study protein folding pathways (Part III Recap)

These first two lectures will be based on the undergraduate protein courses, and will provide a general introduction to the field. Contents will include protein structure determination (NMR, X-ray crystallography, CD, FRET), protein stability calculations (chemical / thermal denaturation) and the characterisation of protein folding pathways and mechanisms (stopped-flow, hydrogen exchange, -values).

AAN 3. Protein folding studies: simple systems AAN 4. Protein folding studies: more complex systems

These two lectures will go beyond the undergraduate course, to look at how it is possible to use a multidisciplinary approach to elucidate detailed mechanistic information about protein folding pathways. Contents will include the study of knotted proteins, characterisation of misfolded proteins, the use of optical tweezers and AFM, the study of co-translational folding, and the identification of cooperativity in multidomain proteins.

SEJ 5. Molecular chaperones: role in biological protein folding and misfolding SEJ 6. Molecular chaperones: therapeutic targets or therapeutic agents?

These two lectures will start by discussing the important differences between protein folding in vitro and protein folding in vivo, and will highlight the need for biological chaperones and the consequences of chaperone disfunction. Contents will include details of ATP-independent chaperones, such as the heat shock proteins and the ATP-dependent chaperones, such as the GroEL/GroES complex. The lectures will finish by looking at the suppression of protein aggregation by natural chaperones and will discuss the possible therapeutic uses of this discovery.

SLS 7. Intrinsically disordered proteins: structure and function SLS 8. Studying the coupled folding and binding of IDPS

These final two lectures will look at a class of proteins that are natively unstructured but biologically active and thus appear to break the structure-function paradigm. Such proteins are not anomalies and indeed recent studies suggest that over 1/3 of proteins in eukaryotic organisms contain intrinsically disordered regions. These lectures will look at the possible reasons for disorder and will suggest why many such proteins are found to be signaling hubs. The course will finish by looking at techniques that can be used to study coupled folding and binding of these proteins and will emphasise the common flaws and misconceptions that hinder such kinetic studies.

Postgraduates in the Department of Chemistry

Number of sessions: 8

Lecture

1 hour