Minimization of the third domain of the LDL receptor-associated protein (RAP) |
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Authors: | Isbell Sara L Haslam Simone B Zankel Todd C |
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Affiliation: | Raptor Pharmaceutical Inc., 9 Commercial Boulevard, Suite 200, Novato, CA 94949, USA. |
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Abstract: | 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. |
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Keywords: | RAP Receptor-associated protein LDLR LRP1 VLDLR Complement-type repeat Domain |
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