[Alpha-2-macroglobulin ligands and their biotransport mechanisms].
Alpha-2-macroglobulin (MG) is a high-molecular weight glycoprotein that possesses a wide range of regulatory functions. Earlier it has been shown that covalent binding of MG with proteinases results in conformational transformation of MG, which enables MG to transport some additional types of cytokines linked by noncovalent interactions. The results of our study have demonstrated that the range of proteins, with the ability for additional binding with transformed MG is variable and comprises IgG, IgA, IgM, albumin, both types of lipoprotein chain, plasmin, some cytokines and even pregnancy associated alpha-2-glycoprotein (structured MG homolog). The major ligands are found to be albumin, IgG, plasmin and, to a lesser degree, lipoproteins. MG interactions with both acidic and low-alkaline proteinases contribute to neutralization of total charge of the formed complex at neutral pH, typical for internal fluids of the organism, and that the addition of low-density lipoprotein receptor-related protein (LRP) increases the amount of electroneutral complexes at pH 7.4. We suppose, that this mechanism enables the transformed MG (or may be its complex with other regulatory proteins) to rapidly precipitate rapidly on cellular surface and then, after binding with LRP and secondary neutralization of the total charge under physiological pH conditions, to pass through cellular membrane and to realize its own regulatory functions.
Zorina
V N
VN
Zorin
N A
NA
Lykova
O F
OF
Konysheva
T V
TV
Zorina
R M
RM
D001693:Biological Transport, Active / Q000502:physiology; D016207:Cytokines / Q000032:analysis / Q000097:blood; D005260:Female; D005341:Fibrinolysin / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis / Q000097:blood; D008024:Ligands; D008074:Lipoproteins / Q000032:analysis / Q000097:blood; D008297:Male; D011247:Pregnancy / Q000097:blood*; D045384:Pregnancy-Associated alpha 2-Macroglobulins / Q000032:analysis / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D012709:Serum Albumin / Q000032:analysis / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000032:analysis / Q000378:metabolism*
D016207:Cytokines; D007136:Immunoglobulins; D008024:Ligands; D008074:Lipoproteins; D045384:Pregnancy-Associated alpha 2-Macroglobulins; D012709:Serum Albumin; D000511:alpha-Macroglobulins; D005341:Fibrinolysin