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Nat Struct Biol. 2001 Mar;8(3):248-53.

The L3 loop and C-terminal phosphorylation jointly define Smad protein trimerization.

Author information

1
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 55 Lake Ave. North, Worcester, Massachusetts 01655, USA.

Abstract

Smad proteins mediate the transforming growth factor beta responses. C-terminal phosphorylation of R-Smads leads to the recruitment of Smad4 and the formation of active signaling complexes. We investigated the mechanism of phosphorylation-induced Smad complex formation with an activating pseudo-phosphorylated Smad3. Pseudo-phosphorylated Smad3 has a greater propensity to homotrimerize, and recruits Smad4 to form a heterotrimer containing two Smad3 and one Smad4. The trimeric interaction is mediated through conserved interfaces to which tumorigenic mutations map. Furthermore, a conserved Arg residue within the L3 loop, located near the C-terminal phosphorylation sites of the neighboring subunit, is essential for trimerization. We propose that the phosphorylated C-terminal residues interact with the L3 loop of the neighboring subunit to stabilize the trimer interaction.

PMID:
11224571
DOI:
10.1038/84995
[Indexed for MEDLINE]

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