Structural and Biochemical Characterization of CIB1 Delineates a New Family of EF-hand-containing Proteins

• Published in: The Journal of biological chemistry 2005-03, Vol.280 (9), p.8407-8415
• Main Authors: Gentry, Holly R, Singer, Alex U, Betts, Laurie, Yang, Cheng, Ferrara, Joseph D, Sondek, John, Parise, Leslie V
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Calcineurin - chemistry; Calcium - chemistry; Calcium - metabolism; Calcium-Binding Proteins - chemistry; Calcium-Binding Proteins - physiology; Chromatography, Gel; Crystallography, X-Ray; Cytoplasm - metabolism; Electrons; Escherichia coli - metabolism; Humans; Ions; Ligands; Models, Molecular; Molecular Sequence Data; Multigene Family; Neurons - metabolism; Peptides - chemistry; Phylogeny; Platelet Glycoprotein GPIIb-IIIa Complex - chemistry; Protein Binding; Protein Conformation; Protein Folding; Protein Structure, Secondary; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Signal Transduction; Ultracentrifugation; X-Rays
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M411515200

CIB1 (CIB) is an EF-hand-containing protein that binds multiple effector proteins, including the platelet αIIbβ3 integrin and several serine/threonine kinases and potentially modulates their function. The crystal structure for Ca 2+ -bound CIB1 has been determined at 2.0 Å resolution and reveals a compact α-helical protein containing four EF-hands, the last two of which bind calcium ions in the standard fashion seen in many other EF-hand proteins. CIB1 shares high structural similarity with calcineurin B and the neuronal calcium sensor (NCS) family of EF-hand-containing proteins. Most importantly, like calcineurin B and NCS proteins, which possess a large hydrophobic pocket necessary for ligand binding, CIB1 contains a hydrophobic pocket that has been implicated in ligand binding by previous mutational analysis. However, unlike several NCS proteins, Ca 2+ -bound CIB1 is largely monomeric whether bound to a relevant peptide ligand or ligand-free. Differences in structure, oligomeric state, and phylogeny define a new family of CIB1-related proteins that extends from arthropods to humans.