3DVE

Crystal Structure of Ca2+/CaM-CaV2.2 IQ domain complex

3DVE の概要

• エントリーDOI: 10.2210/pdb3dve/pdb
• 関連するPDBエントリー: 3DVJ 3DVK 3DVM
• 分子名称: Calmodulin, Voltage-dependent N-type calcium channel subunit alpha-1B, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: calmodulin, calcium channel, iq domain, inactivation, facilitation, calcium-dependent, voltage-gated, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Membrane; Multi-pass membrane protein: Q05152
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 19709.58

構造登録者

Kim, E.Y.,Rumpf, C.H.,Fujiwara, Y.,Cooley, E.S.,Van Petegem, F.,Minor, D.L. (登録日: 2008-07-18, 公開日: 2008-11-04, 最終更新日: 2024-02-21)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.35 Å)