Alpha 2-macroglobulin bait region variants. A role for the bait region in tetramer formation.

The Journal of Biological Chemistry
P G GettinsB C Crews

Abstract

To test the hypothesis that a large portion of the bait region of human alpha 2-macroglobulin (alpha 2M) can be removed without adversely affecting the protein's structural and functional properties, we expressed two human alpha 2M variants with truncated bait regions and examined whether these variants folded normally and functioned as proteinase inhibitors. Each variant contains sites that are normal bait region cleavage sites in wild-type alpha 2M, including the primary trypsin cleavage site. The truncated bait regions are shorter by 23 and 27 residues, respectively, and lack the C-terminal portion as well as different parts of the N-terminal section of the bait region. We found that such bait region truncation permitted normal folding of the monomers as well as formation of the thiol ester and dimerization by disulfide cross-linking, although the resulting species bound 6-(p-toluidino)-2-naphthalenesulfonic acid in a manner more like thiol ester-cleaved alpha 2M than native alpha 2M. The variants' thiol esters reacted with nucleophiles at rates identical to wild-type alpha 2M. Surprisingly, however, the truncations prevented the noncovalent association of the covalent 360-kDa dimers that normally gives tetrameric alpha 2M, ...Continue Reading

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Citations

Apr 26, 2003·Molecular & Cellular Proteomics : MCP·Luca CuculloDamir Janigro
Jun 26, 1995·FEBS Letters·P G GettinsK Hideg
Oct 23, 2012·Journal of Cellular Physiology·Ahmed A RehmanFahim H Khan
May 1, 2019·Viruses·Justin J KurianMavis Agbandje-McKenna

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