title: Structural organization of the receptor associated protein.
abstract: The receptor associated protein (RAP) is a 38 kDa ER-resident protein that binds tightly to the low density lipoprotein receptor-related protein (LRP), and other members of the LDL receptor family of receptors, and competes with all known LRP ligands for binding to LRP. To better understand the domain structure and organization of RAP, we have expressed RAP subfragments and examined them by two-dimensional HSQC NMR and fluorescence spectroscopies, by differential scanning calorimetry, and by both equilibrium and velocity sedimentation measurements. We found that the protein is organized into three domains located in the first third (1D), middle third (2D), and last third (3D) of the protein. All three domains adopt stable tertiary structure as isolated domains and are monomers. Whereas domains 1D and 2D do not interact with one another, 3D interacts with 2D, both in a 2D-3D construct and in intact RAP. Sedimentation measurements also indicated that intact RAP, although monomeric, is significantly elongated.
authors.affiliation: Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60607-7170, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Lazic
authors.forename: Klavs
authors.initials: K
authors.lastname: Dolmer
authors.forename: Dudley K
authors.initials: DK
authors.lastname: Strickland
authors.forename: Peter G W
authors.initials: PG
authors.lastname: Gettins
mesh_terms: D002152:Calorimetry, Differential Scanning; D002499:Centrifugation, Density Gradient; D006801:Humans; D026563:LDL-Receptor Related Protein-Associated Protein / Q000737:chemistry*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000737:chemistry; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry; D017434:Protein Structure, Tertiary; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D026563:LDL-Receptor Related Protein-Associated Protein; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010446:Peptide Fragments