PDBsum entry: 1ijq

Lipid transport

PDB id: 1ijq

Contents

Protein chains

308 a.a. *

Waters ×1180

* Residue conservation analysis

PDB id:

1ijq

Name:

Lipid transport

Title:

Crystal structure of the ldl receptor ywtd-egf domain pair

Structure:

Low-density lipoprotein receptor. Chain: a, b. Fragment: ywtd-e3 domain. Synonym: ldl receptor. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ldlr. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_organ: ovary. Expression_system_cell: cho.

Resolution:

1.50Å R-factor: 0.208 R-free: 0.250

Authors:

H.Jeon,W.Meng,J.Takagi,M.J.Eck,T.A.Springer,S.C.Blacklow

Key ref:

H.Jeon et al. (2001). Implications for familial hypercholesterolemia from the structure of the LDL receptor YWTD-EGF domain pair. Nat Struct Biol, 8, 499-504. PubMed id: 11373616 DOI: 10.1038/88556

Date:

27-Apr-01 Release date: 23-May-01

Protein chains

P01130  (LDLR_HUMAN) -  Low-density lipoprotein receptor

Seq: 860 a.a.

Struc: 308 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: membrane (1 term)

DOI no: 10.1038/88556

Nat Struct Biol 8:499-504 (2001)

PubMed id: 11373616

Implications for familial hypercholesterolemia from the structure of the LDL receptor YWTD-EGF domain pair.

H.Jeon, W.Meng, J.Takagi, M.J.Eck, T.A.Springer, S.C.Blacklow.

ABSTRACT

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.

Selected figure(s)

Figure 2.
Figure 2. Overview of structure and features of propeller blades. a, Ribbon representation of the YWTD domain and adjacent C-terminal EGF-like module (E3) of the LDL receptor, colored to point out the six YWTD repeats of the six-bladed propeller. Left: view down the central axis of the six-bladed propeller; right: side view. Prepared using MOLMOL38. b, Schematic representation of the interactions among consensus residues of each YWTD repeat, following the approach of Sondek et al21. Hydrogen bonds are illustrated with green lines and hydrophobic contacts with red dotted lines. White circles illustrate residues that face toward and pink circles face away from the viewer. The small blue circle represents the position of a water molecule. c, Superposition of the six individual blades from the YWTD propeller. Stereo view in which side chains of conserved residues are illustrated on a ribbon trace of the backbone. d, Stereo view comparison of the second YWTD blade from the LDLR (left) with a WD40 blade from the G seven-bladed propeller21 (right). Side chain and selected backbone hydrogen bonds from conserved Asp and Thr residues of the YWTD blade, and from conserved Asp and His residues of the WD40 blade, are illustrated by dashed light blue lines. Figure prepared using the program InsightII (MSI Inc.).

Figure 4.
Figure 4. Sites of FH mutations mapped onto the structure of the YWTD-EGF domain pair. a, Stereo ribbon trace of the YWTD-E3 structure highlighting the C positions of all sites implicated in FH. The ribbon representing the YWTD domain backbone is khaki-colored, and the ribbon for the EGF module is turquoise. C atoms of FH sites outside of the interdomain interface are colored gray; C of interface sites harboring FH mutations are colored purple. Figure prepared with the program MOLMOL38. b, Close-up of the YWTD-EGF interface region. Side chains of residues in the interface are shown in ball and stick representation, with residues from E3 in blue and residues from the YWTD propeller colored according to atom type. C atoms of interface sites harboring FH mutations are colored purple. Figure prepared with Molscript40.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2001, 8, 499-504) copyright 2001.

Figures were selected by an automated process.