Publisher Summary Turns are a fundamental class of polypeptide structure and are defined as sites where the peptide chain reverses its overall direction. In the past 20 years, the peptide field has witnessed major development, stimulated by the discovery of a host of bioactive peptides. Turn structures have been proposed and implicated in the bioactivity of several of these naturally occurring peptides. In addition, many structural details of turns have been derived from conformational studies of model peptides. During this same period, more than 100 complete protein structures have been elucidated in single-crystal X-ray studies. These examples document the rich diversity of structural patterns in the chain folds of native proteins. Turns are intrinsically polar structures with backbone groups that pack together closely and side chains that project outward. Such an array of atoms may constitute a site for molecular recognition, and indeed, the literature abounds with suggestions that turns serve as loci for receptor binding, antibody recognition, and post-translational modification. In peptides, turns are the conformations of choice for simultaneously optimizing both backbone–chain compactness (intramolecular nonbonded contacts) and side-chain clustering (to facilitate intermolecular recognition). Presence of turns in bioactive conformations may in fact also reflect the lack of alternative conformational possibilities. The aim of this chapter is to examine structural and functional roles of turns in peptides and proteins.

Turns in peptides and proteins.

Publisher Summary The chapter discusses the protein stability with emphasis on compact globular proteins representing a single cooperative system. All the small compact globular proteins represent cooperative systems; they exhibit an extreme cooperativity that integrates the whole of their structure into a single structural unit. The large proteins, to which fibrillar proteins are also related, do not present single cooperative systems, but are subdivided into definite cooperative subsystems—structural blocks or domains. The advances in studying the stability of complicated proteins are connected with two methodical achievements: (1) the appearance of the precise scanning microcalorimetric technique, which affords reliable information on the heat capacity function of proteins in a broad temperature range; and (2) realization of the fact that the complicated heat effect of disruption of a complex macromolecular structure can be analyzed thermodynamically. The thermodynamic specificity of collagen has been considered. The volume of globular proteins does not increase at denaturation but decreases, as seen from their ability to denature under high pressure. The results of calorimetric studies are discussed, presenting the specific melting enthalpy of various protein structures—globular proteins, double-stranded coiled coils, and triplestranded coiled coils. The practical importance of thermodynamic studies of protein stability—that is, its importance not only for understanding the principles of organization of these molecules, but just for obtaining structural information on the domain level is emphasized.

Stability of proteins. Proteins which do not present a single cooperative system

Hydration structure of a collagen peptide.

The molecular conformation of the collagen triple helix confers strict amino acid sequence constraints, requiring a (Gly-X-Y)n repeating pattern and a high content of imino acids. The increasing family of collagens and proteins with collagenous domains shows the collagen triple helix to be a basic motif adaptable to a range of proteins and functions. Its rodlike domain has the potential for various modes of self-association and the capacity to bind receptors, other proteins, GAGs, and nucleic acids. High-resolution crystal structures obtained for collagen model peptides confirm the supercoiled triple helix conformation, and provide new information on hydrogen bonding patterns, hydration, sidechain interactions, and ligand binding. For several peptides, the helix twist was found to be sequence dependent, and such variation in helix twist may serve as recognition features or to orient the triple helix for binding. Mutations in the collagen triple-helix domain lead to a variety of human disorders. The most common mutations are single-base substitutions that lead to the replacement of one Gly residue, breaking the Gly-X-Y repeating pattern. A single Gly substitution destabilizes the triple helix through a local disruption in hydrogen bonding and produces a discontinuity in the register of the helix. Molecular information about the collagen triple helix and the effect of mutations will lead to a better understanding of function and pathology.

Molecular structure of the collagen triple helix.

(1980). Reverse Turns in Peptides and Protein. Critical Reviews in Biochemistry: Vol. 8, No. 4, pp. 315-399.

R.S. Bhatnagar

Papers

A hypothesis on the role of hydroxyproline in stabilizing collagen structure.