The molecular basis for the regulation of the cap-binding complex by the importins.

Publication Type:

Journal Article

Authors:

Dias, Sandra M G; Wilson, Kristin F; Rojas, Katherine S; Ambrosio, Andre L B; Cerione, Richard A

Source:

Nat Struct Mol Biol, Volume 16, Issue 9, p.930-7 (2009)

Keywords:

alpha Karyopherins, Amino Acid Sequence, beta Karyopherins, Crystallography, X-Ray, HeLa Cells, Humans, Models, Molecular, Molecular Sequence Data, Nuclear Cap-Binding Protein Complex, Protein Binding, Protein Structure, Quaternary, Protein Structure, Tertiary, Protein Subunits, RNA Caps

Abstract:

<p>The binding of capped RNAs to the cap-binding complex (CBC) in the nucleus, and their dissociation from the CBC in the cytosol, represent essential steps in RNA processing. Here we show how the nucleocytoplasmic transport proteins importin-alpha and importin-beta have key roles in regulating these events. As a first step toward understanding the molecular basis for this regulation, we determined a 2.2-A resolution X-ray structure for a CBC-importin-alpha complex that provides a detailed picture for how importin-alpha binds to the CBP80 subunit of the CBC. Through a combination of biochemical studies, X-ray crystallographic information and small-angle scattering experiments, we then determined how importin-beta binds to the CBC through its CBP20 subunit. Together, these studies enable us to propose a model describing how importin-beta stimulates the dissociation of capped RNA from the CBC in the cytosol following its nuclear export.</p>