1LDR

SECOND REPEAT OF THE LDL RECEPTOR LIGAND-BINDING DOMAIN

1LDR の概要

• エントリーDOI: 10.2210/pdb1ldr/pdb
• 分子名称: LOW-DENSITY LIPOPROTEIN RECEPTOR (1 entity in total)
• 機能のキーワード: ldl receptor cysteine-rich repeat, binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein: P01130
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4592.01

構造登録者

Daly, N.L.,Djordjevic, J.T.,Kroon, P.A.,Smith, R. (登録日: 1995-08-17, 公開日: 1996-03-08, 最終更新日: 2024-11-06)

主引用文献

Daly, N.L.,Djordjevic, J.T.,Kroon, P.A.,Smith, R.
Three-dimensional structure of the second cysteine-rich repeat from the human low-density lipoprotein receptor.
Biochemistry, 34:14474-14481, 1995

PubMed Abstract: The ligand-binding domain of the low-density lipoprotein receptor comprises seven cysteine-rich repeats, which have been highly conserved through evolution. This domain mediates interactions of the receptor with two lipoprotein apoproteins, apo E and apo B-100, putatively through a calcium-dependent association of the ligands with a cluster of acidic residues on the receptor. The second repeat (rLB2) of the receptor binding domain has been expressed as a thrombin-cleavable GST fusion protein, cleaved, and purified. On oxidation the protein refolded to give a single peak on reverse-phase HPLC. The aqueous solution structure of rLB2 has been determined using two-dimensional 1H NMR spectroscopy. In contrast to the amino-terminal repeat, rLB1, rLB2 has a very flexible structure in water. However, the conformation of rLB2 is markedly more ordered in the presence of a 4-fold molar excess of calcium chloride; the proton resonance dispersion and the number of NOESY cross-peaks are greatly enhanced. The three-dimensional structure of rLB2, obtained from the NMR data by molecular geometry and restrained molecular dynamics methods, parallels that of rLB1, with an amino-terminal hairpin structure followed by a succession of turns. However, there are clear differences in the backbone topology and structural flexibility. As for rLB1, the acidic residues are clustered on one face of the module. The side chain of Asp 37, which is part of a completely conserved SDE sequence thought to be involved in ligand binding, is buried, as is its counterpart (Asp 36) in rLB1. These results provide the first experimental support for the hypothesis that each of the repeats in the ligand-binding domain has a similar global fold but also highlight significant differences in structure and internal dynamics.

PubMed: 7578052
DOI: 10.1021/bi00044a025

実験手法

SOLUTION NMR