The University of Southampton
University of Southampton Institutional Repository

Solution structure of the LDL receptor EGF-AB pair: A paradigm for the assembly of tandem calcium binding EGF domains

Record type: Article

Background: From the observed structure and sequence of a pair of calcium binding (cb) epidermal growth factor-like (EGF) domains from human fibrillin-1, we proposed that many tandem cbEGF domains adopt a conserved relative conformation. The low-density lipoprotein receptor (LDLR), which is functionally unrelated to fibrillin-1, contains a single pair of EGF domains that was chosen for study in the validation of this hypothesis. The LDLR is the protein that is defective in familial hypercholesterolaemia, a common genetic disorder that predisposes individuals to cardiovascular complications and premature death.
Results: Here, we present the solution structure of the first two EGF domains from the LDL receptor, determined using conventional NMR restraints and residual dipolar couplings. The cbEGF domains have an elongated, rod-like arrangement, as predicted. The new structure allows a detailed assessment of the consequences of mutations associated with familial hypercholesterolaemia to be made.
Conclusions: The validation of the conserved arrangement of EGF domains in functionally distinct proteins has important implications for structural genomics, since multiple tandem cbEGF pairs have been identified in many essential proteins that are implicated in human disease. Our results provide the means to use homology modeling to probe structure-function relationships in this diverse family of proteins and may hold the potential for the design of novel diagnostics and therapies in the future.

Full text not available from this repository.

Citation

Saha, S., Boyd, J., Werner, J.M., Knott, V., Handford, P.A., Campbell, I.D. and Downing, A.K. (2001) Solution structure of the LDL receptor EGF-AB pair: A paradigm for the assembly of tandem calcium binding EGF domains Structure, 9, (6), pp. 451-456.

More information

Published date: June 2001

Identifiers

Local EPrints ID: 56162
URI: http://eprints.soton.ac.uk/id/eprint/56162
ISSN: 0969-2126
PURE UUID: b1724219-64ba-47ae-9fea-89d873045934
ORCID for J.M. Werner: ORCID iD orcid.org/0000-0002-4712-1833

Catalogue record

Date deposited: 07 Aug 2008
Last modified: 17 Jul 2017 14:31

Export record

Contributors

Author: S. Saha
Author: J. Boyd
Author: J.M. Werner ORCID iD
Author: V. Knott
Author: P.A. Handford
Author: I.D. Campbell
Author: A.K. Downing

University divisions


Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×