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Knotted proteins: A tangled tale of Structural Biology.

Faísca PF - Comput Struct Biotechnol J (2015)

Bottom Line: Knotted proteins have their native structures arranged in the form of an open knot.Molecular simulations have been playing a fundamental role in this endeavor, and early computational predictions about the knotting mechanism have just been confirmed in wet lab experiments.Here we review a collection of simulation results that allow outlining the current status of the field of knotted proteins, and discuss directions for future research.

View Article: PubMed Central - PubMed

Affiliation: Departament of Physics and BioISI-Biosystems & Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, Lisboa, Portugal.

ABSTRACT
Knotted proteins have their native structures arranged in the form of an open knot. In the last ten years researchers have been making significant efforts to reveal their folding mechanism and understand which functional advantage(s) knots convey to their carriers. Molecular simulations have been playing a fundamental role in this endeavor, and early computational predictions about the knotting mechanism have just been confirmed in wet lab experiments. Here we review a collection of simulation results that allow outlining the current status of the field of knotted proteins, and discuss directions for future research.

No MeSH data available.


Related in: MedlinePlus

The folding rate of protein YibK (a) and YibK fused at one (b,c) or both termini (d) with ThiS. ThiS is a highly stable 91 residue domain (from thermophilic protein from Archaeoglobus fugidus) that hinders threading movements when fused to the chain ends. The measurement of the folding rate indicates that the folding mechanism of this knotted trefoil is based on a threading movement of the C-terminus. Indeed, there is only a drastic decrease of the folding rate when ThiS is fused to the carboxy-terminus. Similar results were reported for YibA (Figure adapted from [86]). Protein chains were prepared with knotplot (http://www.knotplot.com/).
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f0035: The folding rate of protein YibK (a) and YibK fused at one (b,c) or both termini (d) with ThiS. ThiS is a highly stable 91 residue domain (from thermophilic protein from Archaeoglobus fugidus) that hinders threading movements when fused to the chain ends. The measurement of the folding rate indicates that the folding mechanism of this knotted trefoil is based on a threading movement of the C-terminus. Indeed, there is only a drastic decrease of the folding rate when ThiS is fused to the carboxy-terminus. Similar results were reported for YibA (Figure adapted from [86]). Protein chains were prepared with knotplot (http://www.knotplot.com/).

Mentions: More recently, Jackson's in vivo approach to protein folding was used to explore the folding mechanism of proteins YibK and YibA with fused stable domains at the C-terminus, N-terminus or both termini [86] (Fig. 7). The measurement of the folding rate shows very clearly that threading occurs via a mechanism in which the C-terminal end of the chain (which is the shortest knot tail) passes through a loop to form the knot, in strong agreement with predictions from molecular simulations (Fig. 3). Since co-translational folding is the folding process that occurs during protein synthesis, proceeding vectorially from the N-terminus to the C-terminus, these results also indicate that in vivo folding of these particular knotted proteins cannot occur co-translationally. It remains to be experimentally elucidated which exact conformation the C-terminus adopts during the knotting step, which will allow to establish the relative importance of a knotting mechanism based on slipknotting.


Knotted proteins: A tangled tale of Structural Biology.

Faísca PF - Comput Struct Biotechnol J (2015)

The folding rate of protein YibK (a) and YibK fused at one (b,c) or both termini (d) with ThiS. ThiS is a highly stable 91 residue domain (from thermophilic protein from Archaeoglobus fugidus) that hinders threading movements when fused to the chain ends. The measurement of the folding rate indicates that the folding mechanism of this knotted trefoil is based on a threading movement of the C-terminus. Indeed, there is only a drastic decrease of the folding rate when ThiS is fused to the carboxy-terminus. Similar results were reported for YibA (Figure adapted from [86]). Protein chains were prepared with knotplot (http://www.knotplot.com/).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556803&req=5

f0035: The folding rate of protein YibK (a) and YibK fused at one (b,c) or both termini (d) with ThiS. ThiS is a highly stable 91 residue domain (from thermophilic protein from Archaeoglobus fugidus) that hinders threading movements when fused to the chain ends. The measurement of the folding rate indicates that the folding mechanism of this knotted trefoil is based on a threading movement of the C-terminus. Indeed, there is only a drastic decrease of the folding rate when ThiS is fused to the carboxy-terminus. Similar results were reported for YibA (Figure adapted from [86]). Protein chains were prepared with knotplot (http://www.knotplot.com/).
Mentions: More recently, Jackson's in vivo approach to protein folding was used to explore the folding mechanism of proteins YibK and YibA with fused stable domains at the C-terminus, N-terminus or both termini [86] (Fig. 7). The measurement of the folding rate shows very clearly that threading occurs via a mechanism in which the C-terminal end of the chain (which is the shortest knot tail) passes through a loop to form the knot, in strong agreement with predictions from molecular simulations (Fig. 3). Since co-translational folding is the folding process that occurs during protein synthesis, proceeding vectorially from the N-terminus to the C-terminus, these results also indicate that in vivo folding of these particular knotted proteins cannot occur co-translationally. It remains to be experimentally elucidated which exact conformation the C-terminus adopts during the knotting step, which will allow to establish the relative importance of a knotting mechanism based on slipknotting.

Bottom Line: Knotted proteins have their native structures arranged in the form of an open knot.Molecular simulations have been playing a fundamental role in this endeavor, and early computational predictions about the knotting mechanism have just been confirmed in wet lab experiments.Here we review a collection of simulation results that allow outlining the current status of the field of knotted proteins, and discuss directions for future research.

View Article: PubMed Central - PubMed

Affiliation: Departament of Physics and BioISI-Biosystems & Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, Lisboa, Portugal.

ABSTRACT
Knotted proteins have their native structures arranged in the form of an open knot. In the last ten years researchers have been making significant efforts to reveal their folding mechanism and understand which functional advantage(s) knots convey to their carriers. Molecular simulations have been playing a fundamental role in this endeavor, and early computational predictions about the knotting mechanism have just been confirmed in wet lab experiments. Here we review a collection of simulation results that allow outlining the current status of the field of knotted proteins, and discuss directions for future research.

No MeSH data available.


Related in: MedlinePlus