Minimization of the third domain of the LDL receptor-associated protein (RAP)

• Published in: Biochemical and biophysical research communications Vol. 361; no. 3; pp. 758 - 762
• Main Authors: Isbell, Sara L., Haslam, Simone B., Zankel, Todd C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.09.2007
• Subjects: Amino Acid Sequence; Animals; Binding Sites; Cells, Cultured; Complement-type repeat; Domain; LDL-Receptor Related Protein-Associated Protein - chemistry; LDL-Receptor Related Protein-Associated Protein - metabolism; LDLR; Low Density Lipoprotein Receptor-Related Protein-1 - chemistry; Low Density Lipoprotein Receptor-Related Protein-1 - metabolism; LRP1; Mice; Molecular Sequence Data; Peptides - chemical synthesis; Peptides - chemistry; Protein Structure, Tertiary; RAP; Receptor-associated protein; Receptors, LDL - chemistry; Receptors, LDL - metabolism; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Sequence Alignment; VLDLR; RAP; Complement-type repeat; LRP1; VLDLR; Domain; LDLR; Receptor-associated protein
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2007.07.058

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.