2p81
Engrailed homeodomain helix-turn-helix motif
Structural highlights
FunctionHMEN_DROME This protein specifies the body segmentation pattern. It is required for the development of the central nervous system. Transcriptional regulator that represses activated promoters. Wg signaling operates by inactivating the SGG repression of EN autoactivation. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHelices 2 and 3 of Engrailed homeodomain (EnHD) form a helix-turn-helix (HTH) motif. This common motif is believed not to fold independently, which is the characteristic feature of a motif rather than a domain. But we found that the EnHD HTH motif is monomeric and folded in solution, having essentially the same structure as in full-length protein. It had a sigmoidal thermal denaturation transition. Both native backbone and local tertiary interactions were formed concurrently at 4 x 10(5) s(-1) at 25 degrees C, monitored by IR and fluorescence T-jump kinetics, respectively, the same rate constant as for the fast phase in the folding of EnHD. The HTH motif, thus, is an ultrafast-folding, natural protein domain. Its independent stability and appropriate folding kinetics account for the stepwise folding of EnHD, satisfy fully the criteria for an on-pathway intermediate, and explain the changes in mechanism of folding across the homeodomain family. Experiments on mutated and engineered fragments of the parent protein with different probes allowed the assignment of the observed kinetic phases to specific events to show that EnHD is not an example of one-state downhill folding. The helix-turn-helix motif as an ultrafast independently folding domain: the pathway of folding of Engrailed homeodomain.,Religa TL, Johnson CM, Vu DM, Brewer SH, Dyer RB, Fersht AR Proc Natl Acad Sci U S A. 2007 May 29;104(22):9272-7. Epub 2007 May 18. PMID:17517666[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References | ||||||||||||||||||
