Minimization of the third domain of the LDL receptor-associated protein (RAP).
The third domain of the low-density lipoprotein receptor-associated protein (RAP d3) binds with high-affinity to pairs of complement-type repeats (CR) within the LDLR family of receptors. Structural analyses have defined the contact surface between RAP d3 and a CR pair from the low-density lipoprotein receptor (LDLR). Much of the sequence of RAP d3 has been proposed to stabilize the receptor-binding region without participating directly in formation of the contact surface. We have developed a truncated version of RAP d3 in which these scaffolding regions are excised and replaced with a single, intramolecular disulfide bond. This substitution allows for deletion of as much as a third of the RAP d3 sequence with substantial retention of receptor-binding ability.
Isbell
Sara L
SL
Raptor Pharmaceutical Inc., 9 Commercial Boulevard, Suite 200, Novato, CA 94949, USA.
Haslam
Simone B
SB
Zankel
Todd C
TC
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D026563:LDL-Receptor Related Protein-Associated Protein / Q000737:chemistry* / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011973:Receptors, LDL / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
D026563:LDL-Receptor Related Protein-Associated Protein; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010455:Peptides; D011973:Receptors, LDL; D011994:Recombinant Proteins; C036053:VLDL receptor