3OX6

Crystal Structure of the calcium sensor calcium-binding protein 1 (CaBP1)

Summary for 3OX6

• Entry DOI: 10.2210/pdb3ox6/pdb
• Related: 3OX5
• Descriptor: Calcium-binding protein 1, CALCIUM ION, HEXANE-1,6-DIOL, ... (4 entities in total)
• Functional Keywords: ef-hand, calcium-sensor, calcium binding, calcium binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton. Isoform L-CaBP1: Cytoplasm, cytoskeleton. Isoform S-CaBP1: Cytoplasm, cell cortex: Q9NZU7
• Total number of polymer chains: 6
• Total formula weight: 107503.40

Authors

Findeisen, F.,Minor, D.L. (deposition date: 2010-09-21, release date: 2010-12-22, Last modification date: 2024-02-21)

Primary citation

Findeisen, F.,Minor, D.L.
Structural Basis for the Differential Effects of CaBP1 and Calmodulin on Ca(V)1.2 Calcium-Dependent Inactivation.
Structure, 18:1617-1631, 2010

PubMed Abstract: Calcium-binding protein 1 (CaBP1), a calmodulin (CaM) homolog, endows certain voltage-gated calcium channels (Ca(V)s) with unusual properties. CaBP1 inhibits Ca(V)1.2 calcium-dependent inactivation (CDI) and introduces calcium-dependent facilitation (CDF). Here, we show that the ability of CaBP1 to inhibit Ca(V)1.2 CDI and induce CDF arises from interaction between the CaBP1 N-lobe and interlobe linker residue Glu94. Unlike CaM, where functional EF hands are essential for channel modulation, CDI inhibition does not require functional CaBP1 EF hands. Furthermore, CaBP1-mediated CDF has different molecular requirements than CaM-mediated CDF. Overall, the data show that CaBP1 comprises two structural modules having separate functions: similar to CaM, the CaBP1 C-lobe serves as a high-affinity anchor that binds the Ca(V)1.2 IQ domain at a site that overlaps with the Ca²+/CaM C-lobe site, whereas the N-lobe/linker module houses the elements required for channel modulation. Discovery of this division provides the framework for understanding how CaBP1 regulates Ca(V)s.

PubMed: 21134641
DOI: 10.1016/j.str.2010.09.012

Experimental method

X-RAY DIFFRACTION (2.4 Å)