Editors' ChoiceStructural Biology

Unexpected Interaction Between Calcium Channel Subunits

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Science's STKE  15 Jun 2004:
Vol. 2004, Issue 237, pp. tw212-TW212
DOI: 10.1126/stke.2372004TW212

Two groups (Van Petegem et al. and Chen et al.) report crystal structures for the voltage-gated calcium channel regulatory β subunits (Cavβ) and a peptide containing the α-interaction domain (AID) of the pore-forming α subunit. Their results indicate that the interaction site on Cavβ is a hydrophobic cleft in the guanylate kinase (GK) domain, not the previously thought β-interaction domain (BID). The BID is buried in the structures and appears to serve a structural role connecting the various domains (SH3, HOOK, and GK). The AID is located between transmembrane domains I and II and regulates activation, inactivation, G protein modulation, cell surface delivery, and pharmacological properties of the channel. Thus, the β subunits, through their interaction with the AID, contribute to these properties. Van Petegem et al. report that the structure of the Cavβ with AID suggests that binding to Cavβ or a G protein would be mutually exclusive and, based on their relative reported affinities, it is unlikely that a G protein could displace the Cavβ and that G proteins may interact with other cytoplasmic sites on the channel. Because of the domain and structural similarity of Cavβ to PSD95 (a protein involved in scaffolding at synapses), Chen et al. tested whether the PSD95 GK or SH3-HOOK-GK domains could allow calcium channels to traffic to the surface when expressed in Xenopus oocytes. Neither PSD95 construct was competent, and comparison of the GK domain of PSD95 with that of Cavβ showed that the AID binding site is occluded in PSD95.

F. Van Petegem, K. A. Clark, F. C. Chatelain, D. L. Minor, Jr., Structure of a complex between a voltage-gated calcium channel β-subunit and an α-subunit domains. Nature 429, 671-675 (2004). [Online Journal]

Y.-h. Chen, M.-h. Li, Y. Zhang, L.-l. He, Y. Yamada, A. Fitzmaurice, Y. Shen, H. Zhang, L. Tong, J. Yang, Structural basis of the α1-β subunit interaction of voltage-gated Ca2+ channels. Nature 429, 675-680 (2004). [Online Journal]

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