Observation of glycine zipper and unanticipated occurrence of ambidextrous helices in the crystal structure of a chiral undecapeptide

Acharya, Rudresh ; Gupta, Madhvi ; Ramakumar, Suryanarayanarao ; Ramagopal, Udupi A. ; Chauhan, Virander S. (2007) Observation of glycine zipper and unanticipated occurrence of ambidextrous helices in the crystal structure of a chiral undecapeptide BMC Structural Biology, 7 . 51_1-51_9. ISSN 1472-6807

PDF - Publisher Version

Official URL: http://www.biomedcentral.com/1472-6807/7/51

Related URL: http://dx.doi.org/10.1186/1472-6807-7-51


Background: The de novo design of peptides and proteins has recently surfaced as an approach for investigating protein structure and function. This approach vitally tests our knowledge of protein folding and function, while also laying the groundwork for the fabrication of proteins with properties not precedented in nature. The success of these studies relies heavily on the ability to design relatively short peptides that can espouse stable secondary structures. To this end, substitution with α, β-dehydroamino acids, especially α, β-dehydrophenylalanine (ΔPhe) comes in use for spawning well-defined structural motifs. Introduction of ΔPhe induces β-bends in small and 310-helices in longer peptide sequences. Results: The present report is an investigation of the effect of incorporating two glycines in the middle of a ΔPhe containing undecapeptide. A de novo designed undecapeptide, Ac-Gly1-Ala2-ΔPhe3-Leu4-Gly5-ΔPhe6-Leu7-Gly8-ΔPhe9-Ala10-Gly11-NH2, was synthesized and characterized using X-ray diffraction and Circular Dichroism spectroscopic methods. Crystallographic studies suggest that, despite the presence of L-amino acid (L-Ala and L-Leu) residues in the middle of the sequence, the peptide adopts a 310-helical conformation of ambidextrous screw sense, one of them a left-handed (A) and the other a right-handed (B) 310-helix with A and B being antiparallel to each other. However, CD studies reveal that the undecapeptide exclusively adopts a right-handed 310-helical conformation. In the crystal packing, three different interhelical interfaces, Leu-Leu, Gly-Gly and ΔPhe-ΔPhe are observed between the helices A and B. A network of C-H…O hydrogen bonds are observed at ΔPhe-ΔPhe and Gly-Gly interhelical interfaces. An important feature observed is the occurrence of glycine zipper motif at Gly-Gly interface. At this interface, the geometric pattern of interhelical interactions seems to resemble those observed between helices in transmembrane (TM) proteins. Conclusion: The present design strategy can thus be exploited in future work on de novo design of helical bundles of higher order and compaction utilizing ΔPhe residues along with GXXG motif.

Item Type:Article
Source:Copyright of this article belongs to BioMed Central.
ID Code:77427
Deposited On:12 Jan 2012 11:37
Last Modified:18 May 2016 20:42

Repository Staff Only: item control page