HELANAL: A Program to Characterize Helix Geometry in Proteins

Bansal, Manju; Kumar, Sandeep; Velavan, R.

doi:10.1080/07391102.2000.10506570

Cited by 162 publications

(152 citation statements)

References 24 publications

Supporting

Mentioning

150

Contrasting

Order By: Relevance

“…indicators of helix curvature (44,45). For helix-N the average circle diameter and bending angle were 153 Å and 10.1 Ϯ 5.2°, respectively, whereas for helix-C values of 82 Å and 10.7 Ϯ 6.8°, respectively, were obtained.…”

Section: ␣-Synuclein Structure and Dynamicsmentioning

confidence: 96%

“…A static structure for this stretch of helix-N does not reflect the actual dynamic events taking place, but merely describes the effective average conformation of the molecule. However, the elevated dynamics on the microsecond timescale observed for the Lys 45 -Ala 56 region was somewhat surprising given its high S 2 values and large C ␣ secondary shifts, which were comparable to regions with low microsecond timescale dynamics. It follows that, for this region, helical conformation must be maintained throughout any dynamic events taking place.…”

Section: ␣-Synuclein Structure and Dynamicsmentioning

confidence: 99%

“…Effectively, aS absorbs on the micelle surface and alters its surface charge density, a mode of interaction that classifies it as a hydrophobic cation (51). The helixhelix connector exhibited, with Leu 38 , Tyr 39 , Val 40 , Lys 43 , and bordering Lys 45 , a particularly pronounced hydrophobic cationic character (Fig. 7B), which, in turn, may explain its relatively high degree of backbone order on the sub-nanosecond timescale (Fig.…”

Section: ␣-Synuclein Structure and Dynamicsmentioning

confidence: 99%

See 2 more Smart Citations

Structure and Dynamics of Micelle-bound Human α-Synuclein

Ulmer¹,

Bax²,

Cole

et al. 2005

Journal of Biological Chemistry

860

1,168

View full text Add to dashboard Cite

Misfolding of the protein ␣-synuclein (aS), which associates with presynaptic vesicles, has been implicated in the molecular chain of events leading to Parkinson's disease. Here, the structure and dynamics of micelle-bound aS are reported. A dynamic variation in interhelical distance on the microsecond timescale is complemented by enhanced sub-nanosecond timescale dynamics, particularly in the remarkably glycine-rich segments of the helices. These unusually rich dynamics may serve to mitigate the effect of aS binding on membrane fluidity. The well ordered conformation of the helix-helix connector indicates a defined interaction with lipidic surfaces, suggesting that, when bound to larger diameter synaptic vesicles, it can act as a switch between this structure and a previously proposed uninterrupted helix.

show abstract

Section: ␣-Synuclein Structure and Dynamicsmentioning

confidence: 96%

Section: ␣-Synuclein Structure and Dynamicsmentioning

confidence: 99%

Section: ␣-Synuclein Structure and Dynamicsmentioning

confidence: 99%

See 1 more Smart Citation

Structure and Dynamics of Micelle-bound Human α-Synuclein

Ulmer¹,

Bax²,

Cole

et al. 2005

Journal of Biological Chemistry

860

1,168

View full text Add to dashboard Cite

show abstract

“…At least 10 residues in each helix were required for a superposition, and up to 14 residues were considered, if the inclusion of additional residues did not significantly increase the value of the rmsd. Helical angles and interhelical distances were computed from the helical axis vectors identified by using the program HELANAL (28). The angles and distances were computed for the superimposed subsections of the helical pairs, rather than the full helices, which often show irregularities outside of the superimposed regions.…”

Section: Methodsmentioning

confidence: 99%

Helix-packing motifs in membrane proteins

Walters¹,

DeGrado

2006

Proc. Natl. Acad. Sci. U.S.A.

258

279

View full text Add to dashboard Cite

The fold of a helical membrane protein is largely determined by interactions between membrane-imbedded helices. To elucidate recurring helix-helix interaction motifs, we dissected the crystallographic structures of membrane proteins into a library of interacting helical pairs. The pairs were clustered according to their three-dimensional similarity (rmsd <1.5 Å), allowing 90% of the library to be assigned to clusters consisting of at least five members. Surprisingly, three quarters of the helical pairs belong to one of five tightly clustered motifs whose structural features can be understood in terms of simple principles of helix-helix packing. Thus, the universe of common transmembrane helix-pairing motifs is relatively simple. The largest cluster, which comprises 29% of the library members, consists of an antiparallel motif with left-handed packing angles, and it is frequently stabilized by packing of small side chains occurring every seven residues in the sequence. Righthanded parallel and antiparallel structures show a similar tendency to segregate small residues to the helix-helix interface but spaced at four-residue intervals. Position-specific sequence propensities were derived for the most populated motifs. These structural and sequential motifs should be quite useful for the design and structural prediction of membrane proteins.helix-helix packing ͉ protein design ͉ structure prediction H elical transmembrane (TM) proteins are a major class of membrane proteins that are critically involved in functionally rich processes, including bioenergetics, signal transduction, ion transmission, and catalysis. The mechanisms by which TM proteins fold into native structures are beginning to be understood from a confluence of structural and biochemical studies (1-3). The determinants of a membrane protein's fold can be understood by dissecting its structure into pairs of interacting helices, which, together with the connecting loops and extramembrane domains, comprise the overall structure. Along these lines, various workers have examined the geometric characteristics of helix-helix interactions in membrane proteins (4) as well as the features in the amino acid sequences that predispose the helices to adopt these geometries. One outstanding success has been the recognition of the GX 3 G motif, in which Gly (or other small residues) spaced four residues apart mediate a close approach of TM helices (5-7). This motif was first observed in the TM domain of glycophorin A (GpA) (5) and has subsequently been found in both water-soluble (8) and membrane proteins (9). In the classical GpA GX 3 G motif, the helices cross with a right-handed crossing angle of Ϸ40°. In a different TM motif stabilized by ''knobs-into-holes'' packing (10), the helices cross with a smaller left-handed crossing angle.Other surveys of helix-helix packing in membrane proteins have focused on distributions of the interhelical angles, distances, and the composition of the side chains packed at the interface. The helix-helix interfaces tend to be well pa...

show abstract

“…Interhelical angles and axial distances were calculated at the point of minimal axial distance by using the local helical axis. The local helical axes were calculated by using the coordinates of four contiguous C␣ atoms according to Sugeta and Miyazawa (22) with a PERL subroutine adapted from the FORTRAN program HELANAL (23).…”

Section: Methodsmentioning

confidence: 99%

The Cα—H⋅⋅⋅O hydrogen bond: A determinant of stability and specificity in transmembrane helix interactions

Senes

Ubarretxena-Belandia

Engelman

2001

Proc. Natl. Acad. Sci. U.S.A.

463

452

View full text Add to dashboard Cite

The C␣OH⅐⅐⅐O hydrogen bond has been given little attention as a determinant of transmembrane helix association. Stimulated by recent calculations suggesting that such bonds can be much stronger than has been supposed, we have analyzed 11 known membrane protein structures and found that apparent carbon ␣ hydrogen bonds cluster frequently at glycine-, serine-, and threonine-rich packing interfaces between transmembrane helices. Parallel righthanded helix-helix interactions appear to favor C␣OH⅐⅐⅐O bond formation. In particular, C␣OH⅐⅐⅐O interactions are frequent between helices having the structural motif of the glycophorin A dimer and the GxxxG pair. We suggest that C␣OH⅐⅐⅐O hydrogen bonds are important determinants of stability and, depending on packing, specificity in membrane protein folding.T he hydrogen bond is a key element in the interplay between stability and specificity in protein folding. The desolvation penalty associated with burial of polar side chains in an aqueous environment is not always fully recovered by hydrogen bond formation, so hydrogen bonds provide a small or even unfavorable net energy contribution to folding. However, the strength and directionality of hydrogen bonds make them an important factor in discriminating between correctly folded and misfolded states. Hence, polar interactions tend to contribute more to specificity than to stability in soluble proteins (1-3). Conversely, in the apolar environment of biological membranes donor and acceptor groups cannot be satisfied by the solvent, and hydrogen bonds strongly stabilize the helical conformation of membrane spanning domains (4) and can stabilize tertiary interactions as well (5-9). We are interested in the role of hydrogen bonds in the association of transmembrane helices, a stage that is pivotal in the folding of membrane proteins (4). Recently, the DeGrado group and our laboratory showed that the substitution of a single polar amino acid residue into model transmembrane helices induces homooligomerization (10 -13); the association driven by hydrogen bonding can be strong and independent of packing details. Thus, in the apolar environment, the strength of hydrogen bonds can stabilize the association of transmembrane helices, although a lack of a need for sequence specificity could create a danger of inducing promiscuous association (10, 13).Weaker hydrogen bonds, such as those between carbon and oxygen atoms (COH⅐⅐⅐O), have received little attention in the membrane protein field, and their occurrence in membrane proteins has never been surveyed. The C␣ is an activated carbon donor because it is bound to the electron-withdrawing amide NOH and CAO groups, and, in soluble proteins, hydrogen bonds between main-chain C␣OH groups and backbone or side-chain oxygen atoms are often observed (14-17). Despite its abundance, the structural contribution of the C␣OH⅐⅐⅐O hydrogen bond has been unclear and its interaction energy has been believed to be small. Recently, by using ab initio calculations, Vargas et al. (18) and Scheiner et al. (19...

show abstract

HELANAL: A Program to Characterize Helix Geometry in Proteins

Cited by 162 publications

References 24 publications

Structure and Dynamics of Micelle-bound Human α-Synuclein

Structure and Dynamics of Micelle-bound Human α-Synuclein

Helix-packing motifs in membrane proteins

The Cα—H⋅⋅⋅O hydrogen bond: A determinant of stability and specificity in transmembrane helix interactions

Contact Info

Product

Resources

About