Alpha helix how many hydrogen bonds

The CD effect works because proteins are chiral they and their mirror image are different, just like our hands. Depending on the conformation of the main chain, different spectra characteristic for alpha helices or other secondary structures are observed. For more information, take a look at the Birkbeck's PPS2 course. In a similar way, infrared spectroscopy can be used to estimate alpha helical content. One of these properties, the so-called chemical shift, changes slightly depending on the chemical environment an atom is in.

By measuring the chemical shift of the alpha and beta carbon in each amino acid residue, it is possible to predict the secondary structure the residue is part of. However, using the X-ray diffraction pattern of alpha keratin found, for example, in horse hair and chemical insight gained from structures of smaller molecules e.

Historically, finding electron density that fits a helix was used to break this ambiguity. If the helix was right-handed, the electron density was used as is, but if the helix was left-handed, the mirror image was used. To see in which direction an alpha helix goes, you look at the side chain density.

If it points up, the N-terminus is on top, otherwise on the bottom. The following amino acids are rarely found in the center of an alpha helix more than one answer. Category : Pages with quizzes. Alpha helix From Proteopedia. Jump to: navigation , search. Show: Asymmetric Unit Biological Assembly. Export Animated Image.

What level of structure does an alpha helix refer to? The other Gln residues also form these bonds but to a lower extent as indicated, for example, by their side chain chemical shifts. To study this point, we measured the helicity of a peptide based on the sequence of L 4 Q 16 but with all Leu residues mutated to Ala LA , an amino acid that has a smaller side chain and, presumably, a lower ability to shield this hydrogen bond. Despite the higher intrinsic helical propensity of Ala compared to Leu 35 and the higher predicted helicity of LA compared to L 4 Q 16 Supplementary Fig.

This finding confirms that the shielding properties of the Leu side chains are indeed key for the strength of this interaction and for its ability to stabilize polyQ helices. We observed that there was a remarkable loss of dispersion in the 15 N chemical shift dimension for LA: except for the last three Gln residues, all other residues in the tract have the same 15 N chemical shift Fig.

This process can generate a type of bifurcate hydrogen bonding—shown to occur experimentally 37 , 38 and in QM calculations 38 , 39 —that takes advantage of the directionality of the lone pairs of the acceptor group. Specifically, given our results Fig.

The unconventional side chain to main chain bond causes the distribution to shift to longer distances, by 0. Importantly, the total density of the bifurcate hydrogen bond is on average 0.

Furthermore, we have also found that the strength of these bonds is determined by the residue type of the acceptor: Leu residues are good acceptors while Ala residues are not. These results help explaining the residue-specific structural properties of polyQ tracts reported in the recent literature 20 , 42 , The tract of huntingtin also displays some helicity at low pH 42 , 43 , although lower than that observed in the AR. The helical character of the polyQ tract is not homogeneously distributed in either the AR or huntingtin and is instead found to decrease gradually from the N terminus to the C terminus of the tract 20 , 42 , Unless interrupted by residues with a high propensity to accept such bonds, such as Leu, helicity will decay towards the C terminus of the tract.

In addition, our results provide a mechanistic interpretation of the results obtained by Kandel, Hendrickson and co-workers 2 regarding the effect of increasing the coiled coil character of polyQ tracts by interrupting them with Leu residues. Relatively dry environments where phenomena equivalent to this can occur include the core of globular proteins 44 and the interior of cell membranes 45 , as well as amyloid fibrils, where hydrogen bonding interactions involving Gln and Asn side chains parallel to the fibril axis contribute to the stability of the quaternary structure In addition, it has been shown that both exon 1 of huntingtin 47 and the transactivation domain of the AR 48 form condensates that define environments of low dielectric constant, where electrostatic interactions may be strongly favored It will be interesting to address whether this phenomenon plays a role in the highly cooperative liquid—liquid phase separation process of these and similar proteins, as has been proposed to be the case for protein folding, where considering the context-dependent strength of inter-residue interactions proved important for reproducing the high cooperativity of protein folding in lattice simulations PolyQ tracts are frequently found in transcriptional regulators, particularly in transcription factors 1.

In several cases, the transcriptional activity of these molecules has been found to be dependent on the length of the polyQ tracts that they harbor; the physical basis of this phenomenon has, however, not been firmly established to date 1 , Our results provide a plausible rationale as they suggest that variations in the length of polyQ tracts result in changes in the secondary structure of the transactivation domain of transcription factors.

Indeed, such variations can affect the strength of the protein—protein interactions 52 , particularly of those regulating transcription 53 , which include interactions with transcriptional co-regulators and with general transcription factors. Whether a certain change in tract length causes a decrease or an increase in activity might depend on whether the polyQ tract and its flanking regions are involved in interactions with transcriptional co-activators or co-repressors and should therefore be context-dependent, as found experimentally 51 , A number of in vitro experiments have established that the formation of fibrillar aggregates by proteins bearing polyQ tracts can proceed via oligomers 55 , potentially liquid-like 56 , stabilized by intermolecular interactions between flanking regions of polyQ tracts and equivalent to those stabilizing coiled coils 2 , 57 , In proteins bearing polyQ tracts such as huntingtin 59 , 60 and AR 20 , 21 extending the length of the tract increases its helicity and, as we have now shown, that of the sequence immediately flanking them at the N terminus.

Remarkably, this also appears to be the case when they are studied in the context provided by the domains where they are found 20 , 21 and, indeed, in that provided by full-length protein It is therefore conceivable that this extension will change the secondary structure and thus the strength of the interactions that stabilize these oligomers 52 , and, potentially, the rate at which they convert into fibrils.

Our data thus suggest that tract expansion can alter the structure and the stability of the oligomers populated on the fibrillization pathway and consequently modify the rate at which toxic fibrillar species build up In summary, we have shown that side chain to main chain hydrogen bonds donated by Gln side chains can substantially increase the helical propensity of polyQ sequences.

In addition, we found that, for a given sequence context, tract expansion increases helical propensity due to the accumulation of these unconventional interactions. Such hydrogen bonds, that are due to high propensity of the carboxamide group of the Gln side chain to donate hydrogens, are so energetically favored that they can offset the entropic cost of constraining the range of conformations available to the side chain.

In addition, we have shown that the strength of these interactions depends on the degree to which the Gln side chains are exposed to water, implying that the secondary structure of polyQ tracts may vary depending on solution conditions, oligomerization state, and interactions with other molecules.

Our findings provide a plausible mechanistic explanation for the link between polyQ tract length, AR transcriptional activity and solubility, and for the range of AR polyQ tract lengths found in the healthy male population. More generally, they suggest that changes in helicity may underlie the effect of tract length changes on transcriptional activity and on aggregation via helical oligomeric intermediates in polyQ diseases.

In Fig. The eluted fractions containing the His 6 -SUMO-tagged peptides were pooled and dialyzed against the lysis buffer to remove imidazole before digesting them with SUMO protease 0. Cleaved peptides were further purified by a second IMAC step and dialyzed against pure MilliQ water before lyophilization.

The secondary structure of individual frames was analyzed with DSSP 66 , and the chemical shifts were back-calculated with the predictor PPM The trajectories were reweighted to match the experimental chemical shifts by means of a BME method The starting structure was selected from the classical MD simulations of L 4 Q 16 , preserving the previously defined box of water and ions.

The link atoms procedure, as implemented in AMBER program, was used to saturate the valence of the frontier atoms. To classify whether two atoms are hydrogen bonded, we used angle and distance criteria. Specifically, we defined hydrogen bonds as those where the distance between the donor and the acceptor was shorter than 3. After reweighting, we calculated the residue-specific helicity for all of the peptides using the algorithm DSSP From the simulation, the structures that fit this definition were selected and colored on the basis of their average helicity, shown in Fig.

Further information on research design is available in the Nature Research Reporting Summary linked to this article.

Other data are available from the corresponding authors upon reasonable request. Gemayel, R. Variable glutamine-rich repeats modulate transcription factor activity.

Cell 59 , — Fiumara, F. Cell , — Mirkin, S. Expandable DNA repeats and human disease. Nature , — Variable tandem repeats accelerate evolution of coding and regulatory sequences. Lee, J. Sex-specific effects of the Huntington gene on normal neurodevelopment. Cattaneo, E. Orr, H. Trinucleotide repeat disorders. Nalavade, R. Cell Death Dis. Jain, A. RNA phase transitions in repeat expansion disorders. Nagai, Y. A toxic monomeric conformer of the polyglutamine protein. Venkatraman, P. Eukaryotic proteasomes cannot digest polyglutamine sequences and release them during degradation of polyglutamine-containing proteins.

Cell 14 , 95— Schaffar, G. Cellular toxicity of polyglutamine expansion proteins: mechanism of transcription factor deactivation. Cell 15 , 95— Chen, S. Natl Acad. USA 99 , — Yang, W. Aggregated polyglutamine peptides delivered to nuclei are toxic to mammalian cells. Wang, A. Activation of Hsp70 reduces neurotoxicity by promoting polyglutamine protein degradation. Walker, F. Lancet , — Kang, H. Warner, J.

Monomeric huntingtin exon 1 has similar overall structural features for wild-type and pathological polyglutamine lengths. Bennett, M. A linear lattice model for polyglutamine in CAG-expansion diseases. Eftekharzadeh, B. Sequence context influences the structure and aggregation behavior of a polyQ tract.

Davies, P. Consequences of poly-glutamine repeat length for the conformation and folding of the androgen receptor amino-terminal domain. Spada, A. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature , 77—79 Li, M. Nuclear inclusions of the androgen receptor protein in spinal and bulbar muscular atrophy. Giovannucci, E. The CAG repeat within the androgen receptor gene and its relationship to prostate cancer.

USA 94 , — Beilin, J. Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specificity in prostate and non-prostate cell lines. Buchanan, G. Elucidating the folding problem of helical peptides using empirical parameters. Article Google Scholar. Camilloni, C. Determination of secondary structure populations in disordered states of proteins using nuclear magnetic resonance chemical shifts. Biochemistry 51 , — Rangan, R. Determination of structural ensembles of proteins: restraining vs reweighting.

Theory Comput. Bottaro, S. This may be an enthalpic compensation for the greater loss of side-chain conformational entropy for beta-branched amino acids due to the constraint on side-chain torsion angle, namely, chi1, when they occur in helices.

Interestingly, overall propensity for C--H O hydrogen bonds shows that a majority of the helix favoring residues such as Met, Glu, Arg, Lys, Leu, and Gln, which also have large side-chains, prefer to be involved in such types of weak attractive interactions in helices.

The amino acid side-chains that participate in C--H O interactions are found to shield the acceptor carbonyl oxygen atom from the solvent. In addition, C--H O hydrogen bonds are present along with helix stabilizing salt bridges.