3DVK

Crystal Structure of Ca2+/CaM-CaV2.3 IQ domain complex

Summary for 3DVK

• Entry DOI: 10.2210/pdb3dvk/pdb
• Related: 3DVE 3DVJ 3DVM
• Descriptor: Calmodulin, Voltage-dependent R-type calcium channel subunit alpha-1E, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: calmodulin, calcium channel, iq domain, inactivation, facilitation, calcium-dependent, voltage-gated, membrane protein
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Multi-pass membrane protein: Q07652
• Total number of polymer chains: 2
• Total formula weight: 19610.03

Authors

Kim, E.Y.,Rumpf, C.H.,Fujiwara, Y.,Cooley, E.S.,Van Petegem, F.,Minor, D.L. (deposition date: 2008-07-18, release date: 2008-11-04, Last modification date: 2024-02-21)

Primary citation

Kim, E.Y.,Rumpf, C.H.,Fujiwara, Y.,Cooley, E.S.,Van Petegem, F.,Minor, D.L.
Structures of Ca(V)2 Ca(2+)/CaM-IQ Domain Complexes Reveal Binding Modes that Underlie Calcium-Dependent Inactivation and Facilitation.
Structure, 16:1455-1467, 2008

PubMed Abstract: Calcium influx drives two opposing voltage-activated calcium channel (Ca(V)) self-modulatory processes: calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF). Specific Ca(2+)/calmodulin (Ca(2+)/CaM) lobes produce CDI and CDF through interactions with the Ca(V)alpha(1) subunit IQ domain. Curiously, Ca(2+)/CaM lobe modulation polarity appears inverted between Ca(V)1s and Ca(V)2s. Here, we present crystal structures of Ca(V)2.1, Ca(V)2.2, and Ca(V)2.3 Ca(2+)/CaM-IQ domain complexes. All display binding orientations opposite to Ca(V)1.2 with a physical reversal of the CaM lobe positions relative to the IQ alpha-helix. Titration calorimetry reveals lobe competition for a high-affinity site common to Ca(V)1 and Ca(V)2 IQ domains that is occupied by the CDI lobe in the structures. Electrophysiological experiments demonstrate that the N-terminal Ca(V)2 Ca(2+)/C-lobe anchors affect CDF. Together, the data unveil the remarkable structural plasticity at the heart of Ca(V) feedback modulation and indicate that Ca(V)1 and Ca(V)2 IQ domains bear a dedicated CDF site that exchanges Ca(2+)/CaM lobe occupants.

PubMed: 18940602
DOI: 10.1016/j.str.2008.07.010

Experimental method

X-RAY DIFFRACTION (2.3 Å)