INVESTIGADORES
SANCHEZ Maria Cecilia
artículos
Título:
Differential binding properties of Human Pregnancy Zone Protein- and á2-Macroglobulin-proteinase complexes to low density lipoprotein receptor-related protein (LRP)".
Autor/es:
CHIABRANDO GA; VIDES MA; SANCHEZ MC
Revista:
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Editorial:
ELSEVIER SCIENCE INC
Referencias:
Año: 2002 p. 73 - 78
ISSN:
0003-9861
Resumen:
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 PZPproteinase complexes is the low-density lipoprotein receptor-related protein (LRP). Although both a-Mproteinase complexes bind to thesame receptor, differences in the binding propertieshave been reported. In addition, although it is knownthat the binding of a2-Mproteinase complexes to LRPcan be blocked by Ni21, the effect on PZPproteinasehas 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 PZPproteinase complexes to the receptor by enzyme immunoassay. Our results clearly established that although botha-Mproteinase complexes specifically bind to LRP,PZPchymotrypsin complexes bind to the receptorwith lesser apparent affinity (Kd ´ 320 nM) than a2-Mchymotrypsin complexes (Kd ´ 40 nM). We also demonstrated that Ni21 blocks the binding of a2-Mchymotrypsin complexes, but not PZPchymotrypsin 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 PZPproteinase complexes interactwith other receptors not available to a2-Mproteinasecomplexes could be considered. ©