tailieunhanh - Báo cáo khoa học: How does a knotted protein fold?

The issue of how a newly synthesized polypeptide chain folds to form a protein with a unique three-dimensional structure, otherwise known as the ‘protein-folding problem’, remains a fundamental question in the life sci-ences. Over the last few decades, much information has been gathered about the mechanisms by which proteins fold. | ỊFEBS Journal REVIEW ARTICLE How does a knotted protein fold Anna L. Mallam St John s College and University ChemicalLaboratory Cambridge UK Keywords acetohydroxy-acid isomeroreductase dimeric proteins knotted proteins methyltransferases multistate kinetics protein folding topologicalcomplexity topological knots trefoil knot ubiquitin hydrolase Correspondence A. L. Mallam St John s College Cambridge CB2 1TP UK Fax 44 1223 336362 Tel 44 1223 767042 E-mail alm38@ Received 30 September 2008 revised 5 November 2008 accepted 14 November 2008 doi The issue of how a newly synthesized polypeptide chain folds to form a protein with a unique three-dimensional structure otherwise known as the protein-folding problem remains a fundamental question in the life sciences. Over the last few decades much information has been gathered about the mechanisms by which proteins fold. However despite the vast topological diversity observed in biological structures it was thought improbable if not impossible that a polypeptide chain could knot itself to form a functional protein. Nevertheless such knotted structures have since been identified raising questions about how such complex topologies can arise during folding. Their formation does not fit any current folding models or mechanisms and therefore represents an important piece of the protein-folding puzzle. This article reviews the progress made towards discovering how nature codes for and contends with knots during protein folding and examines the insights gained from both experimental and computational studies. Mechanisms to account for the formation of knotted structures that were previously thought unfeasible and their implications for protein folding are also discussed. The protein-folding problem continues to be a major challenge for structural molecular and computational biologists. The past two decades have seen the folding pathways of many proteins characterized in detail using .