Hostname: page-component-78c5997874-v9fdk Total loading time: 0 Render date: 2024-11-02T22:44:34.611Z Has data issue: false hasContentIssue false

NMR structure of a concatemer of the first and second ligand-binding modules of the human low-density lipoprotein receptor

Published online by Cambridge University Press:  01 July 2000

NYOMAN D. KURNIAWAN
Affiliation:
Department of Biochemistry, University of Queensland, QLD 4072, Australia
ANNETTE R. ATKINS
Affiliation:
Department of Biochemistry, University of Queensland, QLD 4072, Australia
STEPHAN BIERI
Affiliation:
Department of Biochemistry, University of Queensland, QLD 4072, Australia
CATHERINE J. BROWN
Affiliation:
Department of Biochemistry, University of Queensland, QLD 4072, Australia
IAN M. BRERETON
Affiliation:
Centre for Magnetic Resonance, University of Queensland, QLD 4072, Australia
PAULUS A. KROON
Affiliation:
Department of Biochemistry, University of Queensland, QLD 4072, Australia
ROSS SMITH
Affiliation:
Department of Biochemistry, University of Queensland, QLD 4072, Australia
Get access

Abstract

The ligand-binding domain of the human low-density lipoprotein receptor consists of seven modules, each of 40–45 residues. In the presence of calcium, these modules adopt a common polypeptide fold with three conserved disulfide bonds. A concatemer of the first and second modules (LB1–2) folds efficiently in the presence of calcium ions, forming the same disulfide connectivities as in the isolated modules. The three-dimensional structure of LB1–2 has now been solved using two-dimensional 1H NMR spectroscopy and restrained molecular dynamics calculations. No intermodule nuclear Overhauser effects were observed, indicating the absence of persistent interaction between them. The near random-coil NH and Hα chemical shifts and the low φ and ψ angle order parameters of the four-residue linker suggest that it has considerable flexibility. The family of LB1–2 structures superimposed well over LB1 or LB2, but not over both modules simultaneously. LB1 and LB2 have a similar pattern of calcium ligands, but the orientations of the indole rings of the tryptophan residues W23 and W66 differ, with the latter limiting solvent access to the calcium ion. From these studies, it appears that although most of the modules in the ligand-binding region of the receptor are joined by short segments, these linkers may impart considerable flexibility on this region.

Type
Research Article
Copyright
2000 The Protein Society

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)