1MR1

Crystal Structure of a Smad4-Ski Complex

Summary for 1MR1

• Entry DOI: 10.2210/pdb1mr1/pdb
• Related: 1YGS
• Descriptor: Mothers against decapentaplegic homolog 4, Ski oncogene, ZINC ION, ... (4 entities in total)
• Functional Keywords: smad, ski, cancer, tgf-b signaling, protein interaction, signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q13485; Nucleus: P12755
• Total number of polymer chains: 4
• Total formula weight: 74453.80

Authors

Wu, J.-W.,Krawitz, A.R.,Chai, J.,Li, W.,Zhang, F.,Luo, K.,Shi, Y. (deposition date: 2002-09-17, release date: 2003-01-21, Last modification date: 2024-02-14)

Primary citation

Wu, J.-W.,Krawitz, A.R.,Chai, J.,Li, W.,Zhang, F.,Luo, K.,Shi, Y.
Structural Mechanism of Smad4 Recognition by the Nuclear Oncoprotein Ski: Insights on Ski-mediated Repression of TGF-beta Signaling
Cell(Cambridge,Mass.), 111:357-367, 2002

PubMed Abstract: The Ski family of nuclear oncoproteins represses TGF-beta signaling through interactions with the Smad proteins. The crystal structure of the Smad4 binding domain of human c-Ski in complex with the MH2 domain of Smad4 reveals specific recognition of the Smad4 L3 loop region by a highly conserved interaction loop (I loop) from Ski. The Ski binding surface on Smad4 significantly overlaps with that required for binding of the R-Smads. Indeed, Ski disrupts the formation of a functional complex between the Co- and R-Smads, explaining how it could lead to repression of TGF-beta, activin, and BMP responses. Intriguingly, the structure of the Ski fragment, stabilized by a bound zinc atom, resembles the SAND domain, in which the corresponding I loop is responsible for DNA binding.

PubMed: 12419246
DOI: 10.1016/S0092-8674(02)01006-1

Experimental method

X-RAY DIFFRACTION (2.85 Å)