%0 Journal Article %J Biochemical Society Transactions %D 2013 %T Identifying knots in proteins. %A Millett, Kenneth C %A Rawdon, Eric J %A Stasiak, Andrzej %A Joanna I. Sulkowska %K Animals %K Humans %K Models, Molecular %K Protein Conformation %K Proteins %X Polypeptide chains form open knots in many proteins. How these knotted proteins fold and finding the evolutionary advantage provided by these knots are among some of the key questions currently being studied in the protein folding field. The detection and identification of protein knots are substantial challenges. Different methods and many variations of them have been employed, but they can give different results for the same protein. In the present article, we review the various knot identification algorithms and compare their relative strengths when applied to the study of knots in proteins. We show that the statistical approach based on the uniform closure method is advantageous in comparison with other methods used to characterize protein knots. %B Biochemical Society Transactions %V 41 %P 533-7 %8 2013 Apr %G eng %N 2 %R 10.1042/BST20120339 %0 Journal Article %J Biochemical Society Transactions %D 2013 %T Knot localization in proteins. %A Rawdon, Eric J %A Millett, Kenneth C %A Joanna I. Sulkowska %A Stasiak, Andrzej %K Animals %K Humans %K Models, Molecular %K Protein Conformation %K Proteins %X The backbones of proteins form linear chains. In the case of some proteins, these chains can be characterized as forming linear open knots. The knot type of the full chain reveals only limited information about the entanglement of the chain since, for example, subchains of an unknotted protein can form knots and subchains of a knotted protein can form different types of knots than the entire protein. To understand fully the entanglement within the backbone of a given protein, a complete analysis of the knotting within all of the subchains of that protein is necessary. In the present article, we review efforts to characterize the full knotting complexity within individual proteins and present a matrix that conveys information about various aspects of protein knotting. For a given protein, this matrix identifies the precise localization of knotted regions and shows the knot types formed by all subchains. The pattern in the matrix can be considered as a knotting fingerprint of that protein. We observe that knotting fingerprints of distantly related knotted proteins are strongly conserved during evolution and discuss how some characteristic motifs in the knotting fingerprints are related to the structure of the knotted regions and their possible biological role. %B Biochemical Society Transactions %V 41 %P 538-41 %8 2013 Apr %G eng %N 2 %R 10.1042/BST20120329 %0 Journal Article %J Biochemical Society Transactions %D 2013 %T Knotting pathways in proteins. %A Joanna I. Sulkowska %A Noel, Jeffrey K %A Ramírez-Sarmiento, César A %A Rawdon, Eric J %A Millett, Kenneth C %A Onuchic, José N %K Animals %K Humans %K Protein Conformation %K Protein Engineering %K Protein Folding %K Proteins %K Thermodynamics %X Most proteins, in order to perform their biological function, have to fold to a compact native state. The increasing number of knotted and slipknotted proteins identified suggests that proteins are able to manoeuvre around topological barriers during folding. In the present article, we review the current progress in elucidating the knotting process in proteins. Although we concentrate on theoretical approaches, where a knotted topology can be unambiguously detected, comparison with experiments is also reviewed. Numerical simulations suggest that the folding process for small knotted proteins is composed of twisted loop formation and then threading by either slipknot geometries or flipping. As the size of the knotted proteins increases, particularly for more deeply threaded termini, the prevalence of traps in the free energy landscape also increases. Thus, in the case of longer knotted and slipknotted proteins, the folding mechanism is probably supported by chaperones. Overall, results imply that knotted proteins can be folded efficiently and survive evolutionary pressure in order to perform their biological functions. %B Biochemical Society Transactions %V 41 %P 523-7 %8 2013 Apr %G eng %N 2 %R 10.1042/BST20120342 %0 Journal Article %J Proceedings of the National Academy of Sciences of the United States of America %D 2012 %T Conservation of complex knotting and slipknotting patterns in proteins. %A Joanna I. Sulkowska %A Rawdon, Eric J %A Millett, Kenneth C %A Onuchic, José N %A Stasiak, Andrzej %K Protein Conformation %K Protein Folding %K Proteins %X While analyzing all available protein structures for the presence of knots and slipknots, we detected a strict conservation of complex knotting patterns within and between several protein families despite their large sequence divergence. Because protein folding pathways leading to knotted native protein structures are slower and less efficient than those leading to unknotted proteins with similar size and sequence, the strict conservation of the knotting patterns indicates an important physiological role of knots and slipknots in these proteins. Although little is known about the functional role of knots, recent studies have demonstrated a protein-stabilizing ability of knots and slipknots. Some of the conserved knotting patterns occur in proteins forming transmembrane channels where the slipknot loop seems to strap together the transmembrane helices forming the channel. %B Proceedings of the National Academy of Sciences of the United States of America %V 109 %P E1715-23 %8 2012 Jun 26 %G eng %N 26 %R 10.1073/pnas.1205918109