Research article

Exon 6 of human JAG1 encodes a conserved structural unit

Alessandro Pintar , Corrado Guarnaccia , Somdutta Dhir and Sándor Pongor

International Centre for Genetic Engineering and Biotechnology (ICGEB), Protein Structure and Bioinformatics Group, AREA Science Park, Padriciano 99, I-34149 Trieste, Italy

author email corresponding author email

BMC Structural Biology 2009, 9:43doi:10.1186/1472-6807-9-43

Published:	8 July 2009

Abstract

Background

Notch signaling drives developmental processes in all metazoans. The receptor binding region of the human Notch ligand Jagged-1 is made of a DSL (Delta/Serrate/Lag-2) domain and two atypical epidermal growth factor (EGF) repeats encoded by two exons, exon 5 and 6, which are out of phase with respect to the EGF domain boundaries.

Results

We determined the ¹H-NMR solution structure of the polypeptide encoded by exon 6 of JAG1 and spanning the C-terminal region of EGF1 and the entire EGF2. We show that this single, evolutionary conserved exon defines an autonomous structural unit that, despite the minimal structural context, closely matches the structure of the same region in the entire receptor binding module.

Conclusion

In eukaryotic genomes, exon and domain boundaries usually coincide. We report a case study where this assertion does not hold, and show that the autonomously folding, structural unit is delimited by exon boundaries, rather than by predicted domain boundaries.