Helix Orientation

Recall that the C-helix contains a strictly conserved glutamic acid residue. It is apparent from multiple structures of different protein kinases that modulation of the conformation of this helix is a common regulatory theme. Additionally, there are multiple ways of regulating C-helix conformation, and as with other modes of regulation, ligand binding is affected. For CDK2 [10, 11], the C-helix is properly 

Other kinases this region is fully accessible, and commonly occupied by inhibitors, so a substantially different binding profile is thus possible for AGC family members, relative to other protein kinases. 

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Bramblett RD, Pann AM, Ballesteros JA, Reggio PH. Construction of 3D model of the cannabinoid CB1 receptor determination of helix ends and helix orientation. Life Sci 1995 56 1971-1982. 

Narayanaswami, V., Maiorano, J. N., Dhanasekaran, P. et al. Helix orientation of the functional domains in apolipoprotein e in discoidal high density lipoprotein particles. /. Biol. Chem. 279 14273-14279, 2004. 

Table 1 Cartesian coordinates (Ang.) of the trisaccharide used to build the double-helix (oriented along the c axis). The three other glucose units of the same strand are generated by the symmetry operation (-x, -y,z+l0.5) and then the other strand is generated by the symmetry operation (-x,-y,z)...

Second, what type of residues are best at the a and d sites This is also a difficult question to answer direcdy because, as will be addressed in more detail over the next few sections, the nature of residues at these sites influences coiled-coil stability, oligomer state, partner selection, and helix-helix orientation (Table I). However, in general terms, natural coiled-coil sequences tend to use the aliphatic hydrophobic residues (Ala, lie, Leu, Met, and Val) at these positions, rather than the aromatic hydrophobic side chains (Phe, Trp and Tyr) (Parry, 1982 Woolfson and Alber, 1995). The reason for this is probably a combination of bulk and steric constraints presented by the aromatic residues. However, a thorough understanding of the possible exclusion of aromatic side chains from coiled-coil... 

Interestingly, when the buried Asn was replaced by Leu, structural specificity was lost and the peptides formed a heterotetramer without fixed helix-helix orientations (Lumb and Kim, 1995). In a further report on this system, Sia and Kim (2001) showed that the two copies of Acid-pl in the heterotetramer could be replaced by a peptide, D-Acid, in which all of the residues were made from D-amino acids. This clever redesign was guided by helical-net diagrams that considered core packing in the D/L structure. These revealed a d rather than a a and d d layers in the core, which were accommodated in the new design by a half-heptad shift of a redesigned L-Base sequence. 

McClain, D. L., Woods, H. L., and Oakley, M. G. (2001). Design and characterization of a heterodimeric coiled coil that forms exclusively with an antiparallel relative helix orientation. / Am. Chem. Soc. 123, 3151-3152. 

FIGURE 4.7 Depiction of a-helix orientation in ATP-gated ion channels... 

Effect of ct-helix orientation on amide I/II ratio and band position... 

To understand spectra in terms of a-helix orientation relative to the water surface, the theoretical normalized PM-IRRAS signal was calculated for an anisotropic polypeptide monolayer, using a general software program [105], The simulation was performed at different orientation angles of the a-helix relative to the water surface [98,106], When the helix axis is parallel to the interface these simulations give a strong positive amide I band and a weak positive amide... 

For most of the embedded dinucleotides, the diphosphate groups are close to the apex of an a helix, oriented towards the binding site of the cofactor. This electrostatic interaction seems to contribute substantially to the binding energy (Section 13.1.2) and could compensate the energy required to unfold the ligand from a compact conformation in solution. 

Fig. 6. Organization of apolipoprotein molecules in discoidal HDL particles. (A) Double belt model for apo A1 structure at the edge of discoidal HDL complex. Two ring-shaped molecules of apo A1 are stacked on top of each other with both molecules in an anti-parallel orientation, allowing the helix registry to maximize intermolecular salt-bridge interactions. Only the charged residues at selected positions are explicitly displayed. (B) Model of apo E in discoidal HDL complex depicting the locations of engineered tryptophan residues on helix 4. Fluorescence from these amino acids was monitored to determine helix orientation. Two out of a total of about four mole-cules/particles of apo E are depicted in which the helical axes are oriented perpendicular to the PL acyl chains.

As the terms internal and external refer to specific positions along a PPII helix oriented against the SH3 surface, it is clear that an inversion of the chain direction will result in the reorientation of the external and internal sites relative to the SH3 surface. If a peptide belongs to class I,... 

An ensemble dynamics approach has been described by Im et al., suitable for deciphering solid-state NMR observables of membrane proteins. Various computational methods for determining transmembrane helix orientations are discussed, and the distributions of VpuTM (from HIV-1) and WALP23 (a synthetic peptide) orientations from solid-state NMR and... 

The dynamics and orientation of a lipophilic drug, trifluoperazine, within model membranes determined by solid-state Helix orientations in membrane-associated Bcl-X-L, an anti-apoptotic protein the function of which is linked to its reversible interaction with mitochondrial outer membranes, determined by... 

Cellulose and its derivatives have the ability to behave both as thermotropic and lyotropic liquid crystals. As mentioned above, several specific phases of liquid crystals occurs, depending on the structure or combination of molecules. In the nematic phase, the molecules have only orientational ordering (making the liquid crystal phase less ordered), while in the smectic phase, the molecules have both orientational and positional ordering [75]. In addition, the optically active molecules can form a chiral nematic phase (or cholesteric phase). In this case, the molecules are helix-oriented generating some spectacular optical properties. 

Tsuboi, M. et al. (2000) Intensity of the polarized Raman band at 1340-1345 cm-1 as an indicator of protein alpha-helix orientation application to Pfl filamentous virus. Biochemistry, 39 (10), 2677 - 2684. 

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