1hj7
From Proteopedia
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==Overview== | ==Overview== | ||
| - | BACKGROUND: From the observed structure and sequence of a pair of calcium | + | 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. |
==Disease== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Campbell, I | + | [[Category: Campbell, I D.]] |
| - | [[Category: Downing, A | + | [[Category: Downing, A K.]] |
| - | [[Category: Handford, P | + | [[Category: Handford, P A.]] |
[[Category: Saha, S.]] | [[Category: Saha, S.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: vldl]] | [[Category: vldl]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:01:47 2008'' |
Revision as of 11:01, 21 February 2008
|
NMR STUDY OF A PAIR OF LDL RECEPTOR CA2+ BINDING EPIDERMAL GROWTH FACTOR-LIKE DOMAINS, 20 STRUCTURES
Contents |
Overview
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.
Disease
Known disease associated with this structure: Hypercholesterolemia, familial OMIM:[606945]
About this Structure
1HJ7 is a Single protein structure of sequence from Homo sapiens with as ligand. Known structural/functional Sites: and . Full crystallographic information is available from OCA.
Reference
Solution structure of the LDL receptor EGF-AB pair: a paradigm for the assembly of tandem calcium binding EGF domains., Saha S, Boyd J, Werner JM, Knott V, Handford PA, Campbell ID, Downing AK, Structure. 2001 Jun;9(6):451-6. PMID:11435110
Page seeded by OCA on Thu Feb 21 13:01:47 2008
Categories: Homo sapiens | Single protein | Campbell, I D. | Downing, A K. | Handford, P A. | Saha, S. | CA | Apo-b | Apo-e | Calcium-binding | Cell-surface receptor | Egf-like domain | Ldl | Module | Vldl
