PDBsum entry: 1ajj

Receptor

PDB id: 1ajj

Contents

Protein chain

37 a.a. *

Ligands

SO4

Metals

_CA

Waters ×30

* Residue conservation analysis

PDB id:

1ajj

Name:

Receptor

Title:

Ldl receptor ligand-binding module 5, calcium-coordinating

Structure:

Low-density lipoprotein receptor. Chain: a. Fragment: ligand-binding domain, fifth repeat. Synonym: lr5. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Resolution:

1.70Å R-factor: 0.209 R-free: 0.240

Authors:

D.Fass,S.C.Blacklow,P.S.Kim,J.M.Berger

Key ref:

D.Fass et al. (1997). Molecular basis of familial hypercholesterolaemia from structure of LDL receptor module. Nature, 388, 691-693. PubMed id: 9262405 DOI: 10.1038/41798

Date:

04-May-97 Release date: 07-Jul-97

Protein chain

P01130  (LDLR_HUMAN) -  Low-density lipoprotein receptor

Seq: 860 a.a.

Struc: 37 a.a.

DOI no: 10.1038/41798

Nature 388:691-693 (1997)

PubMed id: 9262405

Molecular basis of familial hypercholesterolaemia from structure of LDL receptor module.

D.Fass, S.Blacklow, P.S.Kim, J.M.Berger.

ABSTRACT

The low-density lipoprotein receptor (LDLR) is responsible for the uptake of cholesterol-containing lipoprotein particles into cells. The amino-terminal region of LDLR, which consists of seven tandemly repeated, approximately 40-amino-acid, cysteine-rich modules (LDL-A modules), mediates binding to lipoproteins. LDL-A modules are biologically ubiquitous domains, found in over 100 proteins in the sequence database. The structure of ligand-binding repeat 5 (LR5) of the LDLR, determined to 1.7 A resolution by X-ray crystallography and presented here, contains a calcium ion coordinated by acidic residues that lie at the carboxy-terminal end of the domain and are conserved among LDL-A modules. Naturally occurring point mutations found in patients with the disease familial hypercholesterolaemia alter residues that directly coordinate Ca2+ or that serve as scaffolding residues of LR5.

Selected figure(s)

Figure 3.
Figure 3 LR5 Ca^2+coordination compared to ideal octahedral coordination. Red balls indicate positions of coordinating oxygen atoms; the yellow ball shows the position of the Ca^2+ion. Lines are drawn between coordinating atoms in the schematic diagram to show how a six-ligand coordination geometry generates an octahedron. Side chains involved in Ca^2+coordination are superimposed on a ribbon trace of the LR5 backbone. Distances in ring ngströms between coordinating oxygens and the Ca^2+ion are indicated. The figure was generated using Ribbons25. The distances measured in the refined LR5 structure between the side-chain carboxylate groups and the Ca^2+ion are 2.48 0.03 ring . The distances between the backbone carbonyl oxygens and the Ca^2+ion are 2.30 0.03 ring . The r.m.s.d. for the six oxygen atoms coordinating the Ca^2+ion, as compared to an ideal octahedron with centre-to-vertex distances of 2.40 ring , is 0.21 ring , comparable to deviations seen for Ca^2+sites in other proteins26. The octahedral coordination cages the Ca^2+ion such that the folded domain structure is likely to inhibit exchange of the Ca^2+ion with solvent, consistent with the 70 nM Ca^2+-binding affinity of the domain9.

Figure 4.
Figure 4 Surface contours and charge density. a, This orientation of LR5 is similar to that in Fig. 2. The surface-exposed acidic residue on the left is Glu 9. The two regions of basic potential arise from Lys 31 and Lys 33. Glu 16 is above Lys 31 near the centre of this face. The Ca^2+binding site region, towards the upper right, contributes little to the surface charge. b, The hydrophobic face of the molecule is viewed after a rotation of 180° around the vertical. c, A 90° rotation around the horizontal from the orientation in a generates this top view of LR5. The hydrophobic concave face is towards the top of the figure. Regions of basic potential (>16 k[B]T/e, where k[B] is Boltzmann's constant and T is the absolute temperature) are shown in blue; acidic regions (k[B]T/e) are in red. The figure was generated using GRASP27.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (1997, 388, 691-693) copyright 1997.

Figures were selected by an automated process.