Solution structure of the twelfth cysteine-rich ligand-binding repeat in rat megalin

• Published in: Journal of biomolecular NMR Vol. 37; no. 4; pp. 321 - 328
• Main Authors: Wolf, Christian A, Dancea, Felician, Shi, Meichen, Bade-Noskova, Veronika, Rüterjans, Heinz, Kerjaschki, Dontscho, Lücke, Christian
• Format: Journal Article
• Language: English
• Published: Netherlands Dordrecht : Kluwer Academic Publishers 01.04.2007; Springer Nature B.V
• Subjects: Amino Acid Motifs; Amino Acid Sequence; Animals; Calcium - chemistry; Calcium cage; Cysteine - chemistry; Cysteine-rich repeat; LDLR gene family; Ligand-binding domain; Ligands; Low density lipoprotein receptor; Low Density Lipoprotein Receptor-Related Protein-2 - chemistry; Low density lipoprotein receptors; Molecular Sequence Data; Protein Folding; Protein Structure, Secondary; Proteins; Rats; Repetitive Sequences, Nucleic Acid; Rodents; Solutions - chemistry; Static Electricity
• ISSN: 0925-2738; 1573-5001
• DOI: 10.1007/s10858-006-9129-3

Megalin, an approx. 600 kDa transmembrane glycoprotein that acts as multi-ligand transporter, is a member of the low density lipoprotein receptor gene family. Several cysteine-rich repeats, each consisting of about 40 residues, are responsible for the multispecific binding of ligands. The solution structure of the twelfth cysteine-rich ligand-binding repeat with class A motif found in megalin features two short β-strands and two helical turns, yielding the typical fold with a I-III, II-V and IV-VI disulfide bridge connectivity pattern and a calcium coordination site at the C-terminal end. The resulting differences in electrostatic surface potential compared to other ligand-binding modules of this gene family, however, may be responsible for the functional divergence.