Structural and biochemical characterization of CIB1 delineates a new family of EF-hand-containing proteins.
CIB1 (CIB) is an EF-hand-containing protein that binds multiple effector proteins, including the platelet alphaIIbbeta3 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 A resolution and reveals a compact alpha-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.
Gentry
Holly R
HR
Department of Pharmacology, The University of North Carolina, Chapel Hill 27599-7365, USA.
Singer
Alex U
AU
Betts
Laurie
L
Yang
Cheng
C
Ferrara
Joseph D
JD
Sondek
John
J
Parise
Leslie V
LV
D000595:Amino Acid Sequence; D019703:Calcineurin / Q000737:chemistry; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000502:physiology*; D002850:Chromatography, Gel; D018360:Crystallography, X-Ray; D003593:Cytoplasm / Q000378:metabolism; D004583:Electrons; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D007477:Ions; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D009474:Neurons / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010802:Phylogeny; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014461:Ultracentrifugation; D014965:X-Rays
C109198:CIB1 protein, human; D002135:Calcium-Binding Proteins; D007477:Ions; D008024:Ligands; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019703:Calcineurin; D002118:Calcium