1hj7
From Proteopedia
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==Overview== | ==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. | 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. | ||
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| + | ==Disease== | ||
| + | Known disease associated with this structure: Hypercholesterolemia, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606945 606945]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: vldl]] | [[Category: vldl]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:18:46 2007'' |
Revision as of 15:12, 12 November 2007
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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 CA as ligand. Structure known Active Sites: CA1 and CA2. 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 Mon Nov 12 17:18:46 2007
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
