Abstract
The interaction of the serine/threonine kinase Pelle and adaptor protein Tube through their N-terminal death domains leads to the nuclear translocation of the transcription factor Dorsal and activation of zygotic patterning genes during Drosophila embryogenesis. Crystal structure of the Pelle and Tube death domain heterodimer reveals that the two death domains adopt a six-helix bundle fold and are arranged in an open-ended linear array with plastic interfaces mediating their interactions. The Tube death domain has an insertion between helices 2 and 3, and a C-terminal tail making significant and indispensable contacts in the heterodimer. In vivo assays of Pelle and Tube mutants confirmed that the integrity of the major heterodimer interface is critical to the activity of these molecules.
| Original language | English |
|---|---|
| Pages (from-to) | 545-555 |
| Number of pages | 11 |
| Journal | Cell |
| Volume | 99 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 24 1999 |
Funding
We thank Zhiping Liu for her enthusiastic contributions throughout the stages of protein expression and characterization; John J. G. Tesmer for his assistance with data collection and MAD data analysis in addition to his guidance in structure refinement; David E. Coleman for enlightening discussions; Ryan Ulaszek for assistance with site-specific mutagenesis; Lothar Esser with figure preparation; and the staff of the ALS. This work is supported by National Institutes of Health grant GM50545 to S. A. W. and Welch Foundation grant I1229 to S. R. S.
| Funder number |
|---|
| R01GM050545 |
| I1229 |