TIM barrel

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Top view of the triosephosphate isomerase (TIM) barrel (according to PDB  8TIM ), colored from blue ( N terminus) to red ( C terminus).

The TIM barrel (engl. TIM barrel ) is in Biochemistry and Molecular Biology a conserved protein folding , consisting of eight α helices and eight parallel β-strands is that along the peptide backbone alternate. The structure is named after triosephosphate isomerase , a conserved metabolic enzyme. TIM barrels are one of the most common protein folds. One of the features among the members of this class of proteins is that although they all share the same fold in their tertiary structure, there is very little sequence similarity between them. At least 15 different enzyme families use the TIM barrel to generate the appropriate geometry of the active site , always at the C -terminal end of the eight parallel β-strands of the barrel.

Structure and composition

Side view of the TIM barrel (according to PDB  8TIM ).

TIM barrels are considered to be α / β protein folds because they contain an alternating pattern of α helices and β strands in a single domain . In a TIM barrel, the helices and strands (usually 8 each) form a kind of “cylinder coil ” that bends in the form of a “donut”, which is topologically referred to as a toroid , and thus closes itself. The parallel β-strands form the inner wall of the "donut", while the α-helices form the outer wall of the "donut". Each β-strand is connected to the next adjacent strand by a long right-hand loop, the loop containing one of the α-helices. One can also imagine that the TIM keg is made up of 8 overlapping right-handed β-α-β super-secondary structures.

The core of the protein is tightly packed, mostly with bulky hydrophobic amino acid residues, although a few glycines are needed to allow the severely constrained center of the roughly 8 repeats to fit together. The interactions between the strands and helices are also dominated by hydrophobicity and the branched aliphatic residues valine , leucine and isoleucine make up about 40% of the total residues in the β-strands.

In many TIM proteins, the catalytic site and the β-barrel components are more rigid than the helical parts, the positions of which can often vary for certain proteins. An ideal 4x symmetrical TIM barrel enzyme was developed by the Rosetta @ home group using various calculation methods.

Loop regions

Of the approximately 200 residues required to fully form a TIM barrel, approximately 160 are considered structurally equivalent between different proteins that share this fold. The remaining residues are on the loop regions that connect the helices and strands.

The loops at the C -terminal end of the strands tend to contain the active center, which is one reason that this folding occurs frequently. The residues required to maintain the structure and the residues which effect the enzymatic catalysis largely belong to different subgroups. In fact, the loops can be so long that they contain other protein domains. It has recently been shown that catalytic loops can be exchanged between different TIM barrel enzymes as semi-autonomous units of functional groups.

Individual evidence

  1. a b C. Branden, J. Tooze: Introduction to Protein Structure . 2nd Edition. Garland Publishing, New York 1999, ISBN 978-0-8153-2305-1 , pp. 47-50 .
  2. ^ SP Tiwari, N. Reuter: Similarity in Shape Dictates Signature Intrinsic Dynamics Despite No Functional Conservation in TIM Barrel Enzymes. In: PLoS Computational Biology. Volume 12, number 3, March 2016, p. E1004834, doi : 10.1371 / journal.pcbi.1004834 , PMID 27015412 , PMC 4807811 (free full text).
  3. PS Huang, K. Feldmeier, F. Parmeggiani, DA Velasco, B. Höcker, D. Baker: De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy. In: Nature chemical biology. Volume 12, number 1, January 2016, pp. 29-34, doi : 10.1038 / nchembio.1966 , PMID 26595462 , PMC 4684731 (free full text).
  4. ^ A. Ochoa-Leyva, X. Soberón, F. Sánchez, M. Argüello, G. Montero-Morán, G. Saab-Rincón: Protein design through systematic catalytic loop exchange in the (beta / alpha) 8 fold. In: Journal of molecular biology. Volume 387, Number 4, April 2009, pp. 949-964, doi : 10.1016 / j.jmb.2009.02.022 , PMID 19233201 .
  5. A. Ochoa-Leyva, F. Barona-Gómez, G. Saab-Rincón, K. Verdel-Aranda, F. Sánchez, X. Soberón: Exploring the Structure-Function Loop Adaptability of a (β / α) (8) -Barrel Enzyme through Loop Swapping and Hinge Variability. In: Journal of molecular biology. Volume 411, number 1, August 2011, pp. 143–157, doi : 10.1016 / j.jmb.2011.05.027 , PMID 21635898 .