title: The role of a conserved acidic residue in calcium-dependent protein folding for a low density lipoprotein (LDL)-A module: implications in structure and function for the LDL receptor superfamily.
abstract: One common feature of the more than 1,000 complement-type repeats (or low density lipoprotein (LDL)-A modules) found in LDL receptor and the other members of the LDL receptor superfamily is a cluster of five highly conserved acidic residues in the C-terminal region, DXXXDXXDXXDE. However, the role of the third conserved aspartate of these LDL-A modules in protein folding and ligand recognition has not been elucidated. In this report, using a model LDL-A module and several experimental approaches, we demonstrate that this acidic residue, like the other four conserved acidic residues, is involved in calcium-dependent protein folding. These results suggest an alternative calcium coordination conformation for the LDL-A modules. The proposed model provides a plausible explanation for the conservation of this acidic residue among the LDL-A modules. Furthermore, the model can explain why mutations of this residue in human LDL receptor cause familial hypercholesterolemia.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, Illinois 60612, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.forename: Xuemei
authors.initials: X
authors.lastname: Yu
authors.forename: Kayla
authors.initials: K
authors.lastname: Rihani
authors.forename: Qing-Yin
authors.initials: QY
authors.lastname: Wang
authors.forename: Lijun
authors.initials: L
authors.lastname: Rong
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D017124:Conserved Sequence; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017510:Protein Folding; D011973:Receptors, LDL / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D008077:Lipoproteins, LDL; D011973:Receptors, LDL