Tertiary structure, peptide

Section 27 20 The folding of a peptide chain is its tertiary structure The tertiary struc ture has a tremendous influence on the properties of the peptide and the biological role it plays The tertiary structure is normally determined by X ray crystallography... 

A Caflisch, M Karplus. Molecular dynamics studies of protein and peptide folding and unfolding. In K Merz Jr, S Le Grand, eds. The Protein Eoldmg Problem and Tertiary Structure Prediction. Boston Birkhauser, 1994, pp 193-230. 

In the native protein these less stable ds-proline peptides are stabilized by the tertiary structure but in the unfolded state these constraints are relaxed and there is an equilibrium between ds- and trans-isomers at each peptide bond. When the protein is refolded a substantial fraction of the molecules have one or more proline-peptide bonds in the incorrect form and the greater the number of proline residues the greater the fraction of such molecules. Cis-trans isomerization of proline peptides is intrinsically a slow process and in vitro it is frequently the rate-limiting step in folding for those molecules that have been trapped in a folding intermediate with the wrong isomer. 

Shifts in the SEC fractionation range are not new. It has been known for decades that adding chaotropes to mobile phases causes proteins to elute as if they were much larger molecules. Sodium dodecyl sulfate (SDS) (9) and guanidinium hydrochloride (Gd.HCl) (9-12) have been used for this purpose. It has not been clearly determined in every case if these shifts reflect effects of the chaotropes on the solutes or on the stationary phase. Proteins are denatured by chaotropes the loss of tertiary structure increases their hydrodynamic radius. However, a similar shift in elution times has been observed with SEC of peptides in 0.1% trifluoroacetic acid (TEA) (13-15) or 0.1 M formic acid (16), even if they were too small to have significant tertiary structure. Speculation as to the cause involved solvation effects that decreased the effective pore size of the... 

The folding of a single polypeptide chain in three-dimensional space is referred to as its tertiary structure. As discussed in Section 6.2, all of the information needed to fold the protein into its native tertiary structure is contained within the primary structure of the peptide chain itself. With this in mind, it was disappointing to the biochemists of the 1950s when the early protein structures did not reveal the governing principles in any particular detail. It soon became apparent that the proteins knew how they were supposed to fold into tertiary... 

Implicit in the presumption of folding pathways is the existence of intermediate, partially folded conformational states. The notion of intermediate states on the pathway to a tertiary structure raises the possibility that segments of a protein might independently adopt local and well-defined secondary structures (a-helices and /3-sheets). The tendency of a peptide segment to prefer a particular secondary structure depends in turn on its amino acid composition and sequence. 

It is well known that native collagen containes tripeptide sequences, which alone are not capable of building up a triple helix (e.g. Gly-Pro-Leu, Gly-Pro-Ser) when they exist as homopolypeptides. The synthesis of threefold covalently bridged peptide chains opens up the possibility of investigating the folding properties of such weak helix formers, because the bridging reduces the entropy loss during triple-helix formation and thereby increases the thermodynamic stability of the tertiary structure. Therefore, we have... 

It is known that native collagen contains tripeptide sequences which, because of being homopolypeptides, are not able to give rise to triple-helical tertiary structures (e.g. Gly-Pro-Leu, Gly-Pro-Ser). The reason for this and for the above-mentioned low thermostability of the synthetic homopolypeptides is presumably to be found in the fact that in the case of the model peptides with their monotonously repeated tripeptide sequences, special interactions between the side chains of the different amino acid residues as postulated by Ward and Mason are no more possible157). 

In a first step towards the design of / -peptides tyligomers (oligomers that fold into predictable tertiary structures [8]), carefully controlled interhelical hydrophobic interactions have been utilized to stabilize a / -peptide two-helix bundle (92) [179] (Fig. 2.17). 

It is important to note that the secondary and tertiary structure of peptides to which they are attached may subsequently help in controUing the reactivity of... 

However, 2D NOE studies are invaluable in structure determination, in particular of peptides and proteins here the NOEs give invaluable information for conformational analysis and the determination of the tertiary structures of proteins. 

Proteins differ greatly in their intrinsic susceptibility to proteolytic attack. Resistance to proteolysis seems to be dependent upon higher levels of protein structure (i.e. secondary and tertiary structure), as tight packing often shields susceptible peptide bonds from attack. Denaturation thus renders proteins very susceptible to proteolytic degradation. 

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