Peculiaries of interactions between proteins of the macroglobulin family and with the endocytic receptors (a possible mechanism of transmembrane transfer)

Zorina V.N.1 , Zorina R.M.1, Zorin N.A.1

1. Postgraduate Medical Training Institute, Central Research Laboratory
Section: Experimental/Clinical Study
DOI: 10.18097/pbmc20115701106      UDK: 577.122.7      PubMed Id: 21516782
Year: 2011  Volume: 57  Issue: 1  Pages: 106-113
We have conducted a series of experiments, for specification of mechanisms which proteins of the macroglobulin family deliver regulatory substances inside of a cells. We have shown that all members of the family are not only compete for binding to proteinases, but also can interact with each other. We have confirmed that only a complex of alpha-2-macroglobulin (α2-MG) with proteinase is capable to react with the major endocytic receptor (low-density lipoprotein receptor-related protein, LRP). For the first time we have demonstrated, that interaction of α2-MG firstly with proteinase, and then with LRP provokes a progressive conformational consolidation of the multicomplex, which is accompanied by a paradoxical increase of the electrophoretic mobility in comparison with native α2-MG. We suggest that such stepwise conformational consolidation, together with earlier demonstrated charge neutralization (versus pI of internal environments) after interaction firstly with proteinase, and then with LRP, components of is the key moment of the mechanism of transmembrane transfer. Taking into account, that α2-MG transfers a broad spectrum of protein regulators, and interacts not only with LRP, but also with a signal receptor (grp78), and also can regulate (under certain conditions) both own synthesis, and synthesis of LRP and its blocker (receptor - associated protein, RAP), we suggest that this main member of the macroglobulin family plays a leading role in the regulation of intercellular interactions and in the transmission of signal inside of a cell.
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Zorina V.N., Zorina R.M., Zorin N.A. (2011) Biomeditsinskaya khimiya, 57(1), 106-113.
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