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Science 10 December 1999:
Vol. 286. no. 5447, pp. 2119 - 2125
DOI: 10.1126/science.286.5447.2119
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Research Articles

Implication of Tubby Proteins as Transcription Factors by Structure-Based Functional Analysis

Titus J. Boggon, 1 Wei-Song Shan, 2 Sandro Santagata, 3 Samuel C. Myers, 1 Lawrence Shapiro 1*

Tubby-like proteins (TULPs) are found in a broad range of multicellular organisms. In mammals, genetic mutation of tubby or other TULPs can result in one or more of three disease phenotypes: obesity (from which the name "tubby" is derived), retinal degeneration, and hearing loss. These disease phenotypes indicate a vital role for tubby proteins; however, no biochemical function has yet been ascribed to any member of this protein family. A structure-directed approach was employed to investigate the biological function of these proteins. The crystal structure of the core domain from mouse tubby was determined at a resolution of 1.9 angstroms. From primarily structural clues, experiments were devised, the results of which suggest that TULPs are a unique family of bipartite transcription factors.

1 Structural Biology Program, Department of Physiology and Biophysics,
2 Department of Biochemistry and Molecular Biology,
3 Ruttenberg Cancer Center, Mount Sinai School of Medicine of New York University, New York, NY 10029, USA.
*   To whom correspondence should be addressed. E-mail: shapiro{at}anguilla.physbio.mssm.edu

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