Protein secondary stmcture

Fig. 2. Protein secondary stmcture (a) the right-handed a-helix, stabilized by intrasegmental hydrogen-bonding between the backbone CO of residue i and the NH of residue t + 4 along the polypeptide chain. Each turn of the helix requires 3.6 residues. Translation along the hehcal axis is 0.15 nm per residue, or 0.54 nm per turn and (b) the -pleated sheet where the polypeptide is in an extended conformation and backbone hydrogen-bonding occurs between residues on adjacent strands. Here, the backbone CO and NH atoms are in the plane of the page and the amino acid side chains extend from C ...

Rost B et al. Combining evolutionary information and neural networks to predict protein secondary stmcture. Proteins 1994 19 55-72. 

Shaitan, K.V., Mikhailyuk, M.G., Leont ev, K M.,Saraikin, S.S., and Belyakov, A.A. (2002) Molecular dynamics of bending fluctuations of the elements of protein secondary stmcture, Biofizika 47, 411-419. 

The ability of CD spectroscopy to monitor changes in protein secondary stmcture is also used to assess the stabihty... 

Different methods exist that predict protein secondary stmcture elements from chemical shift values [e.g.. Chemical Shift Index (CSI) (3) and Probability-based protein Secondary Stmcture Identification using combined NMR chemical-shift data (PSSI)] (4). These methods are based on the statistics of database analysis of chemical shift values from a range of peptides and proteins of known secondary stmcture. Chemical shifts have also been used to predict backbone torsion angles by software such as Torsion Angle Likelihood Obtained from Shifts and Sequence similarity (TALOS) (5). 

King, R. D. and Sternberg, M. J. E., Identification and application of the concepts important for accurate and reliable protein secondary stmcture prediction, Prot. ScL, 5, 2298, 1996. 

Proof of ROS-mediated DI protein damage is a decrease in electrophoretic mobility of the original Dl protein band." " Most probably it is a consequence of conformational changes in protein secondary stmcture, mainly in the content of the a-helices and P-sheets, as was detected by FTIR spectroscopy in parallel with degradation of the Dl protein.Oxidation of proteins could be confirmed by detection of carbonyl groups that were used as a marker of ROS-mediated protein oxidation." ... 

X-ray crystallography enables information on the tertiary stmcture of proteins up to large molar masses close to atomic resolution, so that at least the spatial positions of the constituting amino acids can be given. From these informations, also portions of the typical protein secondary stmctures a-helix, P-sheet, turns, and random coil can be computed. However, only crystallizable proteins can be analyzed, and the crystal state does not necessarily resemble the solution state, which is closer to its native environment. 

Secondary structure The conformation with respect to nearest neighbor amino acids in a peptide or protein. The a heUx and the pleated P sheet are examples of protein secondary stmctures. 

Secondary structure refers to the local, specific, geometrical shape of a peptide. Hie conformations of peptide backbones are restricted by steric clashes between backbone and side chain atoms. Hie allowed values for the backbone dihedral angles ((p, yi), shown in Figure 1(c), define the spatial orientation of the peptide. Hiis, coupled with the formation of hydrogen bonds between the NH and CO groups of the backbone, leads to regular secondary stmctures, such as the a-helix and the p-sheet, the two most predominant types of protein secondary stmctures. 

The secondary stmcture elements are then identified, and finally, the three-dimensional protein stmcture is obtained from the measured interproton distances and torsion angle parameters. This procedure requites a minimum of two days of nmr instmment time per sample, because two pulse delays are requited in the 3-D experiment. In addition, approximately 20 hours of computing time, using a supercomputer, is necessary for the calculations. Nevertheless, protein stmcture can be assigned using 3-D nmr and a resolution of 0.2 nanometers is achievable. The largest protein characterized by nmr at this writing contained 43 amino acid units (51). However, attempts ate underway to characterize the stmcture of interleukin 2 [85898-30-2] which has over 150 amino acid units. 

Fig. 3. The hierarchy of protein stmctures (a) primary stmcture (see Table 1 for amino acid code) (b) secondary stmcture (c) tertiary stmcture and (d)...

Through combined effects of noncovalent forces, proteins fold into secondary stmctures, and hence a tertiary stmcture that defines the native state or conformation of a protein. The native state is then that three-dimensional arrangement of the polypeptide chain and amino acid side chains that best facihtates the biological activity of a protein, at the same time providing stmctural stabiUty. Through protein engineering subde adjustments in the stmcture of the protein can be made that can dramatically alter its function or stabiUty. 

Fig. 1. The two principal elements of secondary stmcture in proteins, (a) The a-helix stabilized by hydrogen bonds between the backbone of residue i and i + 4. There are 3.6 residues per turn of helix and an axial translation of 150 pm per residue. represents the carbon connected to the amino acid side chain, R. (b) The P sheet showing the hydrogen bonding pattern between neighboring extended -strands. Successive residues along the chain point...

Depending on the predominance of the type of secondary stmcture, proteins can fall into any of three classes. Details are available in Reference 6. 

Attempts have also been made at predicting the secondary stmcture of proteins from the propensities for residues to occur in the a-helix or the P-sheet (23). However, the assignment of secondary stmcture for a residue only has an average accuracy of about 60%. A better success rate (70%) is achieved when multiple-aligned sequences having high sequence similarity are available. 

Even when the secondary stmcture of a protein is known, there are a large number of ways that this stmcture can be packed together. Studies dealing with the identification of the topological constraints in the packing of heUces and sheets have revealed certain patterns, but as of this writing accurate prediction is not possible. 

Simplified models for proteins are being used to predict their stmcture and the folding process. One is the lattice model where proteins are represented as self-avoiding flexible chains on lattices, and the lattice sites are occupied by the different residues (29). When only hydrophobic interactions are considered and the residues are either hydrophobic or hydrophilic, simulations have shown that, as in proteins, the stmctures with optimum energy are compact and few in number. An additional component, hydrogen bonding, has to be invoked to obtain stmctures similar to the secondary stmctures observed in nature (30). 

Secondary Structure. The silkworm cocoon and spider dragline silks are characterized as an antiparaHel P-pleated sheet wherein the polymer chain axis is parallel to the fiber axis. Other silks are known to form a-hehcal (bees, wasps, ants) or cross- P-sheet (many insects) stmctures. The cross-P-sheets are characterized by a polymer chain axis perpendicular to the fiber axis and a higher serine content. Most silks assume a range of different secondary stmctures during processing from soluble protein in the glands to insoluble spun fibers. 

For each fold one searches for the best alignment of the target sequence that would be compatible with the fold the core should comprise hydrophobic residues and polar residues should be on the outside, predicted helical and strand regions should be aligned to corresponding secondary structure elements in the fold, and so on. In order to match a sequence alignment to a fold, Eisenberg developed a rapid method called the 3D profile method. The environment of each residue position in the known 3D structure is characterized on the basis of three properties (1) the area of the side chain that is buried by other protein atoms, (2) the fraction of side chain area that is covered by polar atoms, and (3) the secondary stmcture, which is classified in three states helix, sheet, and coil. The residue positions are rather arbitrarily divided into six classes by properties 1 and 2, which in combination with property 3 yields 18 environmental classes. This classification of environments enables a protein structure to be coded by a sequence in an 18-letter alphabet, in which each letter represents the environmental class of a residue position. 

Proteins that assist folding include protein disulfide isomerase, protine- V,rn2 j,-isomerase, and the chaperones that participate in the folding of over half of mammalian proteins. Chaperones shield newly synthesized polypeptides from solvent and provide an environment for elements of secondary stmcture to emerge and coalesce into molten globules. 

N. Qian and T.J. Sejnowski, Predicting the secondary stmcture of globular proteins using neural network models. J. Molec. Biol., 202 (1988) 568-584. 

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