 |
PDBsum entry 1d2j
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Signaling protein
|
PDB id
|
|
|
|
1d2j
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Solution structure of the sixth ldl-A module of the ldl receptor.
|
|
|
Authors
|
|
C.L.North,
S.C.Blacklow.
|
|
|
Ref.
|
|
Biochemistry, 2000,
39,
2564-2571.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The low-density lipoprotein receptor (LDLR) is the primary mechanism for uptake
of plasma cholesterol into cells and serves as a prototype for an entire class
of cell surface receptors. The amino-terminal domain of the receptor consists of
seven LDL-A modules; the third through the seventh modules all contribute to the
binding of low-density lipoproteins (LDLs). Here, we present the NMR solution
structure of the sixth LDL-A module (LR6) from the ligand binding domain of the
LDLR. This module, which has little recognizable secondary structure, retains
the essential structural features observed in the crystal structure of LDL-A
module five (LR5) of the LDLR. Three disulfide bonds, a pair of buried residues
forming a hydrophobic "mini-core", and a calcium-binding site that serves to
organize the C-terminal lobe of the module all occupy positions in LR6 similar
to those observed in LR5. The striking presence of a conserved patch of negative
surface electrostatic potential among LDL-A modules of known structure suggests
that ligand recognition by these repeats is likely to be mediated in part by
electrostatic complementarity of receptor and ligand. Two variants of LR6,
identified originally as familial hypercholesterolemia (FH) mutations, have been
investigated for their ability to form native disulfide bonds under conditions
that permit disulfide exchange. The first, E219K, lies near the amino-terminal
end of LR6, whereas the second, D245E, alters one of the aspartate side chains
that directly coordinate the bound calcium ion. After equilibration at
physiologic calcium concentrations, neither E219K nor D245E folds to a unique
disulfide isomer, indicating that FH mutations both within and distant from the
calcium-binding site give rise to protein-folding defects.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
Structural independence of ligand-Binding modules five and six of the ldl receptor.
|
|
|
Authors
|
|
C.L.North,
S.C.Blacklow.
|
|
|
Ref.
|
|
Biochemistry, 1999,
38,
3926-3935.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
