Crystal structures of apocalmodulin and an apocalmodulin/SK potassium channel gating domain complex.

Published

Journal Article

Small conductance Ca2+-activated K+ channels (SK channels) are composed of the pore-forming alpha subunit and calmodulin (CaM). CaM binds to a region of the alpha subunit called the CaM binding domain (CaMBD), located intracellular and immediately C-terminal to the inner helix gate, in either the presence or absence of Ca2+. SK gating occurs when Ca2+ binds the N lobe of CaM thereby transmitting the signal to the attached inner helix gate to open. Here we present crystal structures of apoCaM and apoCaM/SK2 CaMBD complex. Several apoCaM crystal forms with multiple (12) packing environments reveal the same EF hand domain-swapped dimer providing potentially new insight into CaM regulation. The apoCaM/SK2 CaMBD structure, combined with our Ca2+/CaM/CaMBD structure suggests that Ca2+ binding induces folding and dimerization of the CaMBD, which causes large CaMBD-CaM C lobe conformational changes, including a >90 degrees rotation of the region of the CaMBD directly connected to the gate.

Full Text

Duke Authors

Cited Authors

  • Schumacher, MA; Crum, M; Miller, MC

Published Date

  • May 2004

Published In

Volume / Issue

  • 12 / 5

Start / End Page

  • 849 - 860

PubMed ID

  • 15130477

Pubmed Central ID

  • 15130477

International Standard Serial Number (ISSN)

  • 0969-2126

Digital Object Identifier (DOI)

  • 10.1016/j.str.2004.03.017

Language

  • eng

Conference Location

  • United States