A straight path to circular proteins.
Folding and stability are parameters that control protein behavior. The possibility of conferring additional stability on proteins has implications for their use in vivo and for their structural analysis in the laboratory. Cyclic polypeptides ranging in size from 14 to 78 amino acids occur naturally and often show enhanced resistance toward denaturation and proteolysis when compared with their linear counterparts. Native chemical ligation and intein-based methods allow production of circular derivatives of larger proteins, resulting in improved stability and refolding properties. Here we show that circular proteins can be made reversibly with excellent efficiency by means of a sortase-catalyzed cyclization reaction, requiring only minimal modification of the protein to be circularized.
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
John M
JM
Antos
Maximilian Wei-Lin
MW
Popp
Robert
R
Ernst
Guo-Liang
GL
Chew
Eric
E
Spooner
Hidde L
HL
Ploegh
D019881:Aminoacyltransferases / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004355:Drug Stability; D005998:Glycine / Q000737:chemistry / Q000378:metabolism; D006033:Glycylglycine / Q000737:chemistry; D006801:Humans; D008970:Molecular Weight; D009842:Oligopeptides / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D011506:Proteins; D006033:Glycylglycine; C035647:glycyl-glycyl-glycine; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases; D005998:Glycine