Implication of Tubby Proteins as Transcription Factors by Structure-Based Functional Analysis.
Boggon, Titus J. 1; Shan, Wei-Song 2; Santagata, Sandro 3; Myers, Samuel C. 1; Shapiro, Lawrence 1*
[Article] Science. 286(5447):2119-2125, December 10, 1999.

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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.

Copyright (C) 1999 by the American Association for the Advancement of Science