Structural basis of the α1–β subunit interaction of voltage-gated Ca2+ channels

Yu-hang Chen, Ming-hui Li, Yun Zhang, Lin-ling He, Yoichi Yamada, Aileen Fitzmaurice, Yang Shen, Hailong Zhang, Liang Tong and Jian Yang ()
Additional contact information
Yu-hang Chen: Columbia University
Ming-hui Li: Columbia University
Yun Zhang: Columbia University
Lin-ling He: Columbia University
Yoichi Yamada: Columbia University
Aileen Fitzmaurice: Columbia University
Yang Shen: Columbia University
Hailong Zhang: Columbia University
Liang Tong: Columbia University
Jian Yang: Columbia University

Nature, 2004, vol. 429, issue 6992, 675-680

Abstract: Abstract High-voltage-activated Ca2+ channels are essential for diverse biological processes. They are composed of four or five subunits, including α1, α2-δ, β and γ (ref. 1). Their expression and function are critically dependent on the β-subunit, which transports α1 to the surface membrane and regulates diverse channel properties2,3,4. It is believed3,4,5,6 that the β-subunit interacts with α1 primarily through the β-interaction domain (BID), which binds directly to the α-interaction domain (AID) of α17; however, the molecular mechanism of the α1–β interaction is largely unclear. Here we report the crystal structures of the conserved core region of β3, alone and in complex with AID, and of β4 alone. The structures show that the β-subunit core contains two interacting domains: a Src homology 3 (SH3) domain and a guanylate kinase (GK) domain. The AID binds to a hydrophobic groove in the GK domain through extensive interactions, conferring extremely high affinity between α1 and β-subunits4,8. The BID is essential both for the structural integrity of and for bridging the SH3 and GK domains, but it does not participate directly in binding α1. The presence of multiple protein-interacting modules in the β-subunit opens a new dimension to its function as a multi-functional protein.

Date: 2004
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature02641 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:429:y:2004:i:6992:d:10.1038_nature02641

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature02641

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().