The structure of receptor-associated protein (RAP).
The receptor-associated protein (RAP) is a molecular chaperone that binds tightly to certain newly synthesized LDL receptor family members in the endoplasmic reticulum (ER) and facilitates their delivery to the Golgi. We have adopted a divide-and-conquer strategy to solve the structures of the individual domains of RAP using NMR spectroscopy. We present here the newly determined structure of domain 2. Based on this structure and the structures of domains 1 and 3, which were solved previously, we utilized experimental small-angle neutron scattering (SANS) data and a novel simulated annealing protocol to characterize the overall structure of RAP. The results reveal that RAP adopts a unique structural architecture consisting of three independent three-helix bundles that are connected by long and flexible linkers. The flexible linkers and the quasi-repetitive structural architecture may allow RAP to adopt various possible conformations when interacting with the LDL receptors, which are also made of repetitive substructure units.
Protein-Nucleic Acid Interaction Section, Structural Biophysics Laboratory, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland 21702, USA.
Donghan
D
Lee
Joseph D
JD
Walsh
Molly
M
Migliorini
Ping
P
Yu
Tao
T
Cai
Charles D
CD
Schwieters
Susan
S
Krueger
Dudley K
DK
Strickland
Yun-Xing
YX
Wang
D001665:Binding Sites; D026563:LDL-Receptor Related Protein-Associated Protein / Q000737:chemistry*; D008958:Models, Molecular; D033363:Neutron Diffraction; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D053838:Scattering, Small Angle
D026563:LDL-Receptor Related Protein-Associated Protein