RAP Protein (Stable Variant) LRP1 Antagonist

Stable Receptor-Associated Protein (RAP/LRPAP1) is an engineered recombinant protein used as an antagonist of LRP1 (low-density lipoprotein receptor-related protein 1). This stable RAP construct contains mutations that increase resistance to pH- and heat-induced denaturation, allowing high-affinity binding to LRP1 and inhibition of LRP1 function in vitro and in vivo.

Contributors

Inventor Institute
Dudley K. Strickland University of Maryland
Cat. #: 153996
Tool sub type: Inhibitor
Research Fields: Cell signaling and signal transduction;Disease (not cancer);Metabolism;Other
Application: Inhibits LRP1 function
Alternate name: receptor-associated protein
Product description: Receptor-Associated Protein (RAP) is a chaperone of LRP1 (lipoprotein receptor-related protein 1). Usually, at low pHs the D3 domain unfolds and RAP dissociates from LRP1. In contrast, this RAP was engineered by Prasad et al. 2015, to overcome this. A disulfide bond was introduced to RAP, resulting in a stable RAP, which allows high affinity binding to LRP1. As a result, this RAP is an effective inhibitor of LRP1 activity. This stable RAP is resistant to both pH and heat denaturation. It has been shown to be a potent inhibitor or LRP1 function in both in vitro and in vivo.  To stabilise the RAP, the following mutations were made: H257F, H259F, Y260C, H268F, H290F, T297C.  LRP1 is an endocytic receptor that interacts with several ligands including alpha 2-macroglobulin. Functionally, the receptor mediates cellular signalling with implications in Alzheimer's disease. This receptor is expressed in brain, liver, and lung and localized to the cytoplasm and nucleus. Expression of LRP1 requires RAP, a molecular chaperone of LRP1. 
Additional notes: This RAP protein was engineered to resist pH and heat-induced denaturation via the addition of a disulfide bond within the D3 domain and elimination of key histidine residues. This stable RAP molecule does not disassociate from LRP1 under acidic conditions and thus functions as a potent LRP1 antagonist both in-vitro and in-vivo.
Molecular weight: 38kDa
Animal free: Yes
References:

Prasad et al. 2015. J Biol Chem. 290(28):17262-8. PMID: 26013822.

Generation of a Potent Low Density Lipoprotein Receptor-related Protein 1 (LRP1) Antagonist by Engineering a Stable Form of the Receptor-associated Protein (RAP) D3 Domain.

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