Defining immunomodulatory interactions of alpha1-antitrypsin in vivo with biophysical, structural, proteomic and cell biological studies


The protein alpha1-antitrypsin has important anti-inflammatory roles.  Some of these relate to its best-understood function (protease inhibition), but others do not.  Thus we have recently characterized a central role for alpha1-antitrypsin in immune cell responses to VitaminD.  Our data support the importance of a direct interaction between alpha1-antitrypsin and a complement component.  This project will characterise the interaction by mass-spectrometry, NMR and crystallographic studies of ex vivo and recombinant samples. We will also search for further alpha1-antitrypsin:cytokine interactions of pathophysiological relevance MS proteomics of patient samples and healthy controls.  We will assess pathophysiological relevance by immune cell biology studies.

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Structural dynamics associated with intermediate formation in an archetypal conformational disease MP Nyon, L Segu, LD Cabrita, G Lévy, J Kirkpatrick, BD Roussel, AOM Patschull, R Kerr, UI Ekeowa, TE Barrett, N Kalsheker, M Hill, K Thalassinos, DA Lomas, J Christodoulou, B Gooptu Structure 2012, 20:504-12


Conformational pathology of the serpins – themes, variations and therapeutic strategies B Gooptu and DA Lomas Annual Review of Biochemistry 2009, 78:147-176


A Comparison of Labeling and Label-Free Mass Spectrometry-Based Proteomics Approaches VJ Patel†, K Thalassinos, Slade, S. E., Connolly, J. B., Crombie, A., Murrell, J. C. and Scrivens, J. H. † joint first authors Journal of Proteome Research (2009) 8:3752-3759

Biological Areas:

Structural Biology


Molecules, cells and industrial biotechnology