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The structure of receptor‐associated protein (RAP)
Author(s) -
Lee Donghan,
Walsh Joseph D.,
Migliorini Molly,
Yu Ping,
Cai Tao,
Schwieters Charles D.,
Krueger Susan,
Strickland Dudley K.,
Wang YunXing
Publication year - 2007
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.072865407
Subject(s) - substructure , endoplasmic reticulum , golgi apparatus , receptor , protein structure , structural motif , crystallography , biophysics , chemistry , biology , biochemistry , engineering , structural engineering
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.