1ijq
From Proteopedia
Crystal Structure of the LDL Receptor YWTD-EGF Domain Pair
Contents |
Overview
The low-density lipoprotein receptor (LDLR) is the primary mechanism for uptake of cholesterol-carrying particles into cells. The region of the LDLR implicated in receptor recycling and lipoprotein release at low pH contains a pair of calcium-binding EGF-like modules, followed by a series of six YWTD repeats and a third EGF-like module. The crystal structure at 1.5 A resolution of a receptor fragment spanning the YWTD repeats and its two flanking EGF modules reveals that the YWTD repeats form a six-bladed beta-propeller that packs tightly against the C-terminal EGF module, whereas the EGF module that precedes the propeller is disordered in the crystal. Numerous point mutations of the LDLR that result in the genetic disease familial hypercholesterolemia (FH) alter side chains that form conserved packing and hydrogen bonding interactions in the interior and between propeller blades. A second subset of FH mutations are located at the interface between the propeller and the C-terminal EGF module, suggesting a structural requirement for maintaining the integrity of the interdomain interface.
Disease
Known disease associated with this structure: Hypercholesterolemia, familial OMIM:[606945]
About this Structure
1IJQ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Implications for familial hypercholesterolemia from the structure of the LDL receptor YWTD-EGF domain pair., Jeon H, Meng W, Takagi J, Eck MJ, Springer TA, Blacklow SC, Nat Struct Biol. 2001 Jun;8(6):499-504. PMID:11373616 Page seeded by OCA on Fri May 2 20:04:33 2008
