Protein helix bundles

Conformational free energy simulations are being widely used in modeling of complex molecular systems [1]. Recent examples of applications include study of torsions in n-butane [2] and peptide sidechains [3, 4], as well as aggregation of methane [5] and a helix bundle protein in water [6]. Calculating free energy differences between molecular states is valuable because they are observable thermodynamic quantities, related to equilibrium constants and... 

E. M. Boczko and C. L. Brooks III. First principles calculation of the folding free energy of a three helix bundle protein. Science, 269 393-396, 1995. 

Fig. 5. Protein folding. The unfolded polypeptide chain coUapses and assembles to form simple stmctural motifs such as -sheets and a-hehces by nucleation-condensation mechanisms involving the formation of hydrogen bonds and van der Waal s interactions. Small proteins (eg, chymotrypsin inhibitor 2) attain their final (tertiary) stmcture in this way. Larger proteins and multiple protein assembhes aggregate by recognition and docking of multiple domains (eg, -barrels, a-helix bundles), often displaying positive cooperativity. Many noncovalent interactions, including hydrogen bonding, van der Waal s and electrostatic interactions, and the hydrophobic effect are exploited to create the final, compact protein assembly. Further stmctural...

Other approaches to de novo four-helix bundle proteins have emphasized nonrepetitive designs. One such example is the four-helix bundle protein Felix (53), a 79-residue protein which uses 19 of the 20 naturally occurring amino acids ... 

The four-helix bundle is a common domain structure in a proteins... 

Figure 3.6 Four-helix bundles frequently occur as domains in a proteins. The arrangement of the a helices is such that adjacent helices in the amino acid sequence are also adjacent in the three-dimensional structure. Some side chains from all four helices are buried in the middle of the bundle, where they form a hydrophobic core, (a) Schematic representation of the path of the polypeptide chain in a four-helrx-bundle domain. Red cylinders are a helices, (b) Schematic view of a projection down the bundle axis. Large circles represent the main chain of the a helices small circles are side chains. Green circles are the buried hydrophobic side chains red circles are side chains that are exposed on the surface of the bundle, which are mainly hydrophilic.

In most four-helix bundle structures, including those shown in Figure 3.7, the a helices are packed against each other according to the "ridges in grooves" model discussed later in this chapter. However, there are also examples where coiled-coil dimers packed by the "knobs in holes" model participate in four-helix bundle structures. A particularly simple illustrative example is the Rop protein, a small RNA-binding protein that is encoded by certain plasmids and is involved in plasmid replication. The monomeric sub unit of Rop is a polypeptide chain of 63 amino acids built up from two... 

The coiled-coil structure of the leucine zipper motif is not the only way that homodimers and heterodimers of transcription factors are formed. As we saw in Chapter 3 when discussing the RNA-binding protein ROP, the formation of a four-helix bundle structure is also a way to achieve dimerization, and the helix-loop-helix (HLH) family of transcription factors dimerize in this manner. In these proteins, the helix-loop-helix region is preceded by a sequence of basic amino acids that provide the DNA-binding site (Figure 10.23), and... 

Alpha helices D and E from the L and M subunits (Figure 12.14) form the core of the membrane-spanning part of the complex. These four helices are tightly packed against each other in a way quite similar to the four-helix bundle motif in water-soluble proteins. Each of these four helices provides a histidine side chain as ligand to the Ee atom, which is located between the helices close to the cytoplasm. The role of the Ee atom is probably to... 

Figure 17.10 Construction of a two helix truncated Z domain, (a) Diagram of the three-helix bundle Z domain of protein A (blue) bound to the Fc fragment of IgG (green). The third helix stabilizes the two Fc-binding helices, (b) Three phage-display libraries of the truncated Z-domaln peptide were selected for binding to the Fc. First, four residues at the former helix 3 interface ("exoface") were sorted the consensus sequence from this library was used as the template for an "intrafece" library, in which residues between helices 1 and 2 were randomized. The most active sequence from this library was used as a template for five libraries in which residues on the Fc-binding face ("interface") were randomized. Colored residues were randomized blue residues were conserved as the wild-type amino acid while yellow residues reached a nonwild-type consensus, [(b) Adapted from A.C. Braisted and J.A. Wells,...

They started from the sequence of a domain, Bl, from an IgG-binding protein called Protein G. This domain of 56 amino acid residues folds into a four-stranded p sheet and one a helix (Figure 17.16). Their aim was to convert this structure into an all a-helical structure similar to that of Rop (see Chapter 3). Each subunit of Rop is 63 amino acids long and folds into two a helices connected by a short loop. The last seven residues are unstructured and were not considered in the design procedure. Two subunits of Rop form a four-helix bundle (Figure 17.16). 

DeGrado, W.F., Regan, L., Ho, S.P. The design of a four-helix bundle protein. Cold Spring Harbor Symp. Quant. Biol. 52 521-526, 1987. 

Antiparallel tt-helix proteins are structures heavily dominated by a-helices. The simplest way to pack helices is in an antiparallel manner, and most of the proteins in this class consist of bundles of antiparallel helices. Many of these exhibit a slight (15°) left-handed twist of the helix bundle. Figure 6.29 shows a representative sample of antiparallel a-helix proteins. Many of these are regular, uniform structures, but in a few cases (uteroglobin, for example) one of the helices is tilted away from the bundle. Tobacco mosaic virus protein has small, highly... 

A helix bundle is a protein composed of a series of rodlike helical domains linked by flexible segments and inserted into a membrane to form a cluster of helices roughly parallel to one another and perpendicular to the plane of the membrane. 

In 1996, the 3D-structure of D. vulgaris Rr was published by de-Mare and collaborators 48), and all the studies earlier published were proved to be correct. The protein is described as a tetramer of two-domain subunits (Fig. 4). Each subunit contains a domain characterized by a four-helix bundle surrounding a diiron-oxo site and a C-terminal rubredoxin-like Fe(RS)4 domain (see Fig. 2). In this last do-... 

Berriz GF, Shakhnovich El. Characterization of the folding kinetics of a three-helix bundle protein via a minimalist Langevin model. J Mol Biol 2001 310 673-85. 

Markosyan RM, Cohen FS, Melikyan GB. HIV-1 envelope proteins complete their folding into six-helix bundles immediately after fusion pore formation. Mol Biol Cell 2003 14(3) 926—938. 

The N-terminal domain of the OCP is an orthogonal alpha-helical bundle, subdivided into two four-helix bundles (Figure 1.3a and c). These subdomains are composed of discontinuous segments of the polypeptide chain (gray and white in Figure 1.3c). To date, the OCP N-terminal domain is the only known protein structure with this particular fold (Pfam 09150). The hydroxyl terminus of the 3 -hydroxyechinenone is nestled between the two bundles. The C-terminal domain (dark... 

The CP MAS NMR spectroscopy has been also extensively used for studies of proteins containing retinylidene chromophore like proteorhodopsin or bacteriorhodopsin. Bacteriorhodopsin is a protein component of purple membrane of Halobacterium salinarium.71 7 This protein contains 248 amino acids residues, forming a 7-helix bundle and a retinal chromophore covalently bound to Lys-216 via a Schiff base linkage. It is a light-driven proton pump that translocates protons from the inside to the outside of the cell. After photoisomerization of retinal, the reaction cycle is described by several intermediate states (J, K, L, M, N, O). Between L and M intermediate states, a proton transfer takes place from the protonated Schiff base to the anionic Asp85 at the central part of the protein. In the M and/or N intermediate states, the global conformational changes of the protein backbone take place. 

L. inocua ferritin site however, is the first described so far that has ligands belonging to two different subunits, and is not contained within a four-helix bundle. Recently it has been suggested that the neutrophil-activating protein of Helicobacter pylori, the major antigen of the immune response in infected individuals, is also a dodecameric ferritin, capable of binding up to 500 iron atoms per oligomer (Tonello et ah, 1999). 

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