Backbone dynamics of a module pair from the ligand-binding domain of the LDL receptor.
The ligand-binding domain of the LDL receptor consists of seven contiguous LDL-A modules. The fifth of these ligand-binding modules is absolutely required for recognition of both LDL and beta-VLDL particles. A four-residue linker of variable sequence connects each pair of modules, except for modules four and five, which are connected by a 12-residue linker. To provide a more detailed understanding of the structural relationship in a typical pair of functionally important LDL-A repeats of the LDLR, we investigated the backbone dynamics of repeats five (LR5) and six (LR6) alone and in the context of the covalently connected LR5-6 pair. Our results reveal substantial flexibility in the four-residue linker connecting the two repeats in the LR5-6 pair. The intrinsic dynamic behavior of each repeat is essentially unchanged when the repeats are covalently connected. These observations indicate that the relative orientation of repeats in LR5-6 is not fixed. Modeled in an extended conformation, the linker can separate LR5 and LR6 by up to 15 A, a distance that would allow substantial freedom of motion of each repeat with respect to the other in the pair.
Beglova
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Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.
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Blacklow
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D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D009587:Nitrogen Isotopes; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011973:Receptors, LDL / Q000737:chemistry* / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D012996:Solutions; D013816:Thermodynamics
D008024:Ligands; D009587:Nitrogen Isotopes; D010446:Peptide Fragments; D011973:Receptors, LDL; D012996:Solutions