Probing the stability of native and activated forms of alpha2-macroglobulin.

Published

Journal Article

alpha2-Macroglobulin (alpha2M) is a 718 kDa homotetrameric proteinase inhibitor which undergoes a large conformational change upon activation. This conformational change can occur either by proteolytic attack on an approximately 40 amino acid stretch, the bait region, which results in the rupture of the four thioester bonds in alpha2M, or by direct nucleophilic attack on these thioesters by primary amines. Amine activation circumvents both bait region cleavage and protein incorporation, which occurs by proteolytic activation. These different activation methods allow for examination of the roles bait region cleavage and thioester rupture play in alpha2M stability. Differential scanning calorimetry and urea gel electrophoresis demonstrate that both bait region cleavage and covalent incorporation of protein ligands in the thioester pocket play critical roles in the stability of alpha2M complexes.

Full Text

Duke Authors

Cited Authors

  • Kaczowka, SJ; Madding, LS; Epting, KL; Kelly, RM; Cianciolo, GJ; Pizzo, SV

Published Date

  • January 1, 2008

Published In

Volume / Issue

  • 42 / 1

Start / End Page

  • 62 - 67

PubMed ID

  • 17996290

Pubmed Central ID

  • 17996290

International Standard Serial Number (ISSN)

  • 0141-8130

Digital Object Identifier (DOI)

  • 10.1016/j.ijbiomac.2007.09.019

Language

  • eng

Conference Location

  • Netherlands