A New Class of Regulatory Motifs for Gi-subunit

Through bioinformatics and structural analysis, the authors of this paper have identified an evolutionary conserved motifs in calcium binding proteins, Nucleobindin-1 and -2.

G protein binding sites on Calnuc (nucleobindin 1) and NUCB2 (nucleobindin 2) define a new class of Gαi-regulatory motifs.
M Garcia-Marcos, PS Kietrsunthorn, H Wang, P Ghosh & MG Farquhar. 2011. JBC in press
Department of Cellular and Molecular Medicine, George Palade Laboratories of Cellular and Molecular Medicine, University of California, San Diego, USA.


The calcium binding proteins are:

Nucleobindin-1 (aka CALNUC) is a major calcium binding protein of the Golgi, involved in calcium homeostasis.

Nucleobindin-2 (gene name: NUCB2) is a calcium binding protein, possibly involved in calcium homeostasis; it has a broader, cellular distribution than the above.

The two are reported to shares 62% sequence identity.

The conserved motif identified has a similarity to GEF sequence of Girdin (aka GIV) , a multifunctional protein that has been reported to interact with Gαi/0/s but not with Gαq/11/12/13 (Le-Niculescu et al. 2005).

The motif was shown to be evolutionally conserved in those proteins, from invertebrates to humans.

Both Nucleobindin-1 and -2 were demonstrated to bind preferentially to Gαi3 at its inactive state.

They have also shown that Gαi3 binding likely occurs when the Nucleobindin-1 or -2 are in calcium-unbound state.


Ref.

Le-Niculescu H et al. 2005. Identification and Characterization of GIV, a Novel Gαi/s-interacting Protein Found on COPI, Endoplasmic Reticulum-Golgi Transport VesiclesJ Biol Chem 280: 22012-22020