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.
January 2007
BMC Structural Biology;2007, Vol. 7, p51
Academic Journal
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.


Related Articles

  • Conformation Analysis of Ile-Ala-Val-Pro Peptide and Its Derivatives by Circular Dichroism. Pak, V. V.; Koo, M. S.; Kwon, D. Y.; Kasirnova, T. D. // Chemistry of Natural Compounds;Jul/Aug2004, Vol. 40 Issue 4, p398 

    Ile-Ala-Val-Pro as a hypocholesterolemic peptide was isolated from soybean protein. We have synthesized four peptides, Ile-Ala- Val-P ro-Gly-Glu- Val-Ala, Leu-Ile-Ala-Val-Pro-Gly-Glu-Val-Ala, Ile-Ala-Val-Pro-Thr-Gly-Val-Ala, Leu-Ile-Ala-Val-Pro-Thr-Gly-Val-Ala, with a conserved Ile-Ala-Val-Pro...

  • Structures of Ovine Corticotropin-Releasing Factor and Its Ala32 Mutant as Studied by CD and NMR Techniques. Ryu, Kyoung-Seok; Choi, Byong-Seok; Chi, Seung-Wook; Kim, Seung-Ho; Kim, Hyoungman // Journal of Biochemistry;2000, Vol. 127 Issue 4, p687 

    The corticotropin-releasing factor (CRF) is a 41-amino acid peptide-amide hormone, which mediates a general stress-response. It has been reported that the substitution of His-32 in the ovine CRF (oCRF) with Ala brings about a 4.5-fold increase in activity [Kornreich et at (1992) J. Med Chem. 35,...

  • The Unfolding of α-Momorcharin Proceeds Through the Compact Folded Intermediate. Fukunaga, Yukihiro; Nishimoto, Etsuko; Otosu, Takuhiro; Murakami, Yasutaka; Yamashita, Shoji // Journal of Biochemistry;Oct2008, Vol. 144 Issue 4, p457 

    The unfolding of α-momorcharin was systematically investigated using steady-state and time-resolved tryptophan fluorescence, circular dichroism and 8-anilino-1-naphthalenesulfonic acid (ANS) binding. These spectroscopic studies demonstrated that α-momorcharin unfolded through a compact...

  • Computational biology: Protein predictions. Dodson, Eleanor J. // Nature;11/8/2007, Vol. 450 Issue 7167, p176 

    The article discusses the study that assesses the three-dimensional structure of proteins from its amino-acid sequence through X-ray diffraction and nuclear magnetic resonance (NMR). The peptide sequence is mapped against the existing information, and energy profile of each atom is incorporated...

  • Structural Features of the Peptide Homologous to 6-25 Fragment of Influenza A PB1 Protein. Egorov, Vladimir V.; Matusevich, Oleg V.; Shaldzhyan, Aram A.; Skvortsov, Alexey N.; Zabrodskaya, Yana A.; Garmay, Yuri P.; Landa, Sergey B.; Lebedev, Dmitry V.; Zarubayev, Vladimir V.; Sirotkin, Alexey K.; Vasin, Andrey V.; Kiselev, Oleg I. // International Journal of Peptides;2013, p1 

    A mirror-symmetry motif was discovered in the N-terminus of the influenza virus PB1 protein. Structure of peptide comprised of the corresponding part of PB1 (amino acid residues 6-25) was investigated by circular dichroism and in silico modeling. We found that peptide PB1 (6-25) in solution...

  • pH-induced equilibrium unfolding of apomyoglobin: Substitutions at conserved Trp14 and Met131 and non-conserved Val17 positions. Dyuysekina, A. E.; Dolgikh, D. A.; Samatova, E. N.; Tiktopulo, E. I.; Balobanov, V. A.; Bychkova, V. E. // Biochemistry (00062979);Jun2008, Vol. 73 Issue 6, p693 

    A number of residues in globins family are well conserved but are not directly involved in the primary oxygen-carrying function of these proteins. A possible role for these conserved, non-functional residues has been suggested in promoting a rapid and correct folding process to the native...

  • Stereospecific binding of a disordered peptide segment mediates BK channel inactivation. Gonzalez-Perez, Vivian; Zeng, Xu-Hui; Henzler-Wildman, Katie; Lingle, Christopher J. // Nature;5/3/2012, Vol. 485 Issue 7396, p133 

    A number of functionally important actions of proteins are mediated by short, intrinsically disordered peptide segments, but the molecular interactions that allow disordered domains to mediate their effects remain a topic of active investigation. Many K+ channel proteins, after initial channel...

  • Prediction of Protein Secondary Structure Content by Using the Concept of Chou's Pseudo Amino Acid Composition and Support Vector Machine. Chao Chen; Lixuan Chen; Xiaoyong Zou; Peixiang Cai // Protein & Peptide Letters;Jan2009, Vol. 16 Issue 1, p27 

    Protein secondary structure carries information about local structural arrangements. Significant majority of successful methods for predicting the secondary structure is based on multiple sequence alignment. However, the multiple alignment fails to achieve accurate results when a protein...

  • Rapid crystallization of glycine using metal-assisted and microwave-accelerated evaporative crystallization: the effect of engineered surfaces and sample volume. Grell, Tsehai A. J.; Pinard, Melissa A.; Pettis, Danielle; Aslan, Kadir // Nano Biomedicine & Engineering;2012, Vol. 4 Issue 3, p125 

    Metal-Assisted and Microwave-Accelerated Evaporative Crystallization (MA-MAEC), is a new approach to crystallization of drug compounds, amino acids, DNA and proteins. In this work, we report our additional findings on the effect of engineered surfaces and sample volume on the rapid...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics