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Establishing the role of alpha-2-macoglobulin in quality control of extracellular protein folding

Grant


Scheme


  • Discovery Projects

Abstract


  • Extracellular protein misfolding underpins a variety of serious human diseases (e.g. Alzheimer's disease). Control of extracellular protein folding is likely to involve extracellular chaperones directing misfolded client proteins to cell surface receptors for uptake and degradation. We recently showed that the abundant human blood protein alpha-2-macroglobulin (A2M) has both protease inhibitor and chaperone activities. We aim to (i) further characterise the chaperone activities of A2M, (ii) define interactions between A2M-misfolded client protein complexes and cell surface receptors, and (iii) show that these interactions are integral to an in vivo disposal mechanism for damaged proteins.

Date/time Interval


  • 2009

Sponsor Award Id


  • DP0984341

Local Award Id


  • 10222

Scheme


  • Discovery Projects

Abstract


  • Extracellular protein misfolding underpins a variety of serious human diseases (e.g. Alzheimer's disease). Control of extracellular protein folding is likely to involve extracellular chaperones directing misfolded client proteins to cell surface receptors for uptake and degradation. We recently showed that the abundant human blood protein alpha-2-macroglobulin (A2M) has both protease inhibitor and chaperone activities. We aim to (i) further characterise the chaperone activities of A2M, (ii) define interactions between A2M-misfolded client protein complexes and cell surface receptors, and (iii) show that these interactions are integral to an in vivo disposal mechanism for damaged proteins.

Date/time Interval


  • 2009

Sponsor Award Id


  • DP0984341

Local Award Id


  • 10222