David Auble
Some eukaryotic proteins don't have obvious orthologs and their origin has been a puzzle. Several global regulators of transcription and chromatin structure fall into this category. Aravind and Koonin (Curr Biol 8:R111–R113, 1998) offered one provocative solution when they observed sequence similarity between two such transcription/chromatin factors and some aminopeptidases. Intriguingly, this similarity did not extend to peptidase residues that are critical for catalytic activity. The idea was that some transcription factors were derived from ancient peptidases. In this case, the peptidase fold is utilized for protein binding, but since the catalytic residues have been lost, the transcription factors have no peptidase activity. Structural support has been obtained for this idea. Spt16 is one of the proteins predicted to have a peptidase fold. The N-terminal domain of S. pombe Spt16 (3cb5) is shown below. The structure of the Spt16 N-terminal domain is strikingly similar to the structure of bacterial prolidase and creatinase. The structure of creatinase (1chm) is shown below for comparison. How close is the similarity in the two structures? The relationship was discovered by structural homology search which revealed extensive alignment of ~300 Cα atoms extending over their entire "catalytic" domains (rmsd < 2.5 angstroms). In the report of the Spt16 N-terminal domain structure, the authors also show that this domain interacts with histones H3 and H4, so the fold is used for protein-protein interaction rather than for some other purpose.
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3cb5 |
1chm |
Index of Macromolecular Structures