Differential binding properties of Human Pregnancy Zone Protein- and á2-Macroglobulin-proteinase complexes to low density lipoprotein receptor-related protein (LRP)".

CHIABRANDO GA; VIDES MA; SANCHEZ MC

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

ELSEVIER SCIENCE INC

Año: 2002 p. 73 - 78

0003-9861

Human pregnancy zone protein (PZP) is a majorpregnancy-associated plasma protein strongly relatedto a2-macroglobulin (a2-M). Both a-macroglobulins (aMs) covalently bind proteinases, which is accompanied by the exposure of carboxy terminal receptorrecognition domains important for the rapid clearance from the circulation and tissues. It is acceptedthat the molecule responsible for the clearance ofa2-M– and PZP–proteinase complexes is the low-density lipoprotein receptor-related protein (LRP). Although both a-M–proteinase complexes bind to thesame receptor, differences in the binding propertieshave been reported. In addition, although it is knownthat the binding of a2-M–proteinase complexes to LRPcan be blocked by Ni21, the effect on PZP–proteinasehas never been examined. In order to investigate differences in the binding properties of both a-Ms to thereceptor, we purified LRP from human placenta byaffinity chromatography and then analyzed the specificity and affinity of binding of a2-M– and PZP–proteinase complexes to the receptor by enzyme immunoassay. Our results clearly established that although botha-M–proteinase complexes specifically bind to LRP,PZP–chymotrypsin complexes bind to the receptorwith lesser apparent affinity (Kd ´ 320 nM) than a2-M–chymotrypsin complexes (Kd ´ 40 nM). We also demonstrated that Ni21 blocks the binding of a2-M–chymotrypsin complexes, but not PZP–chymotrypsin complexes, to LRP. These data suggest that the binding toLRP involves conformational differences betweenboth a-Ms in a region immediately upstream of thecarboxy terminal receptor recognition domain. Thepossibility that PZP–proteinase complexes interactwith other receptors not available to a2-M–proteinasecomplexes could be considered. ©