Thematic Minireview Series on Circular Proteins

David J Craik,Norma M Allewell

doi:10.1074/jbc.r112.390344

Abstract

Circular proteins have now been discovered in all kingdoms of life and are characterized by their exceptional stability and the diversity of their biological activities, primarily in the realm of host defense functions. This thematic minireview series provides an overview of the distribution, evolution, activities, and biological synthesis of circular proteins. It also reviews approaches that biological chemists are taking to develop synthetic methods for making circular proteins in the laboratory. These approaches include solid-phase peptide synthesis based on an adaption of native chemical ligation technology and recombinant DNA approaches that are amenable to the in-cell production of cyclic peptide libraries. The thioester-mediated native chemical ligation approach mimics, to some extent, elements of the natural biosynthetic reaction, which, for disulfide-rich cyclic peptides, appears to involve asparaginyl endopeptidase-mediated processing from larger precursor proteins.

Highlights

Conventional proteins are synthesized on the ribosome as topologically linear chains of amino acids that typically fold into complex three-dimensional shapes that are determined by the linear sequence of amino acids
Like many previously known cyclic peptides, cyclosporin is biosynthesized by complex peptide synthetases that typically incorporate non-proteogenic amino acids
The biosynthetic pathways of cyclotides and other plant cyclic peptides are not yet fully understood, but it is clear that they are processed from precursor proteins and that asparaginyl endoproteinases, which are cysteine proteases, have an important role in the processing and cyclization [4, 5]

Summary

Introduction

Conventional proteins are synthesized on the ribosome as topologically linear chains of amino acids that typically fold into complex three-dimensional shapes that are determined by the linear sequence of amino acids. These biochemical advantages benefit the organism that produces the circular protein in its native environment and are advantageous when circular proteins are used in agricultural, diagnostic, or pharmaceutical applications, where stability, potency, and target selectivity are important attributes. This series of minireviews describes the discovery, biological activities, biosynthesis, and applications of circular proteins in

Results

Conclusion