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PDBsum entry 4rtd
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Lipid binding protein
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PDB id
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4rtd
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References listed in PDB file
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Key reference
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Title
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Structure of protease-Cleaved escherichia coli α-2-Macroglobulin reveals a putative mechanism of conformational activation for protease entrapment.
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Authors
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C.D.Fyfe,
R.Grinter,
I.Josts,
K.Mosbahi,
A.W.Roszak,
R.J.Cogdell,
D.M.Wall,
R.J.Burchmore,
O.Byron,
D.Walker.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2015,
71,
1478-1486.
[DOI no: ]
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PubMed id
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Abstract
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Bacterial α-2-macroglobulins have been suggested to function in defence as
broad-spectrum inhibitors of host proteases that breach the outer membrane.
Here, the X-ray structure of protease-cleaved Escherichia coli
α-2-macroglobulin is described, which reveals a putative mechanism of
activation and conformational change essential for protease inhibition. In this
competitive mechanism, protease cleavage of the bait-region domain results in
the untethering of an intrinsically disordered region of this domain which
disrupts native interdomain interactions that maintain E. coli
α-2-macroglobulin in the inactivated form. The resulting global conformational
change results in entrapment of the protease and activation of the thioester
bond that covalently links to the attacking protease. Owing to the similarity in
structure and domain architecture of Escherichia coli α-2-macroglobulin and
human α-2-macroglobulin, this protease-activation mechanism is likely to
operate across the diverse members of this group.
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