Bioinformatics Analysis of the Periodicity in Proteins with Coiled-Coil Structure-Enumerating All Decompositions of Sequence Periods

Abstract

A coiled coil is a structural motif in proteins that consists of at least two α-helices wound around each other. For structural stabilization, these α-helices form interhelical contacts via their amino acid side chains. However, there are restrictions as to the distances along the amino acid sequence at which those contacts occur. As the spatial period of the α-helix is 3.6, the most frequent distances between hydrophobic contacts are 3, 4, and 7. Up to now, the multitude of possible decompositions of α-helices participating in coiled coils at these distances has not been explored systematically. Here, we present an algorithm that computes all non-redundant decompositions of sequence periods of hydrophobic amino acids into distances of 3, 4, and 7. Further, we examine which decompositions can be found in nature by analyzing the available data and taking a closer look at correlations between the properties of the coiled coil and its decomposition. We find that the availability of decompositions allowing for coiled-coil formation without putting too much strain on the α-helix geometry follows an oscillatory pattern in respect of period length. Our algorithm supplies the basis for exploring the possible decompositions of coiled coils of any period length.

Keywords: aldehyde dehydrogenase; coiled coil; decomposition algorithm; hexaprenyl diphosphate synthase; hydrophobic interaction; money-changing problem; recursive algorithm; seduheptulose-7-phosphate isomerase.

Figure 1

Comparison of the number of theoretically possible decompositions (red) and decompositions found in dimeric coiled coils listed in the CC+-database (blue) for period lengths between 3 to 40. Be aware that the y-axis (number of decompositions) is log-transformed.

Figure 2

Decompositions not containing repeats of interhelical contact residue distances of 3 or 4 longer than two.

Figure 3

Comparison of structural properties between coiled coils with demanding (at least one repeat of interhelical contact distance 3 or 4) and non-demanding decompositions. (A): Comparing the highest local period deviation, i.e., the highest deviation along the coiled coil from the base periodicity of 3.5 Å. (B): Comparing the difference between the maximum local periodicity and the minimum periodicity along the coiled-coil structure. (C): Comparing the difference between the maximum local radius and the minimum local radius along the coiled-coil structure.

Figure 4

Local periodicity and local radius for the 25 identified demanding decompositions. The abscissa shows the amino acid sequence. The amino acids that are part of the 3 + 3 or 4 + 4 hydrophobic distance repeats within the decompositions are surrounded by a red box. Amino acids participating in interhelical contacts are further underlaid by a red circle. The three dots at the end of an amino acid sequence range indicate that the full coiled-coil sequence according to the CC+-database is deprecated in the CCdb.

Figure 5

PDB-ID 3aqc, the ligand-bound form of 3aqb. (A): Detailed view on the coiled coil. The red α-helix realizes the demanding [4, 3, 3]-decomposition. The blue α-helix is the interaction partner for the formation of the coiled coil. (B) Shows a total view on the protein with different colors for its subunits. (C): Amino acid sequence of the coiled-coil range analyzed by the CCdb. (D): Complete sequence of the α-helix. Contact residues of the coiled coil are bold. The contact residues of the [3, 3]-repeat are colored in magenta, corresponding to (A).

Figure 6

PDB-ID 5i01. (A): Detailed view on the coiled coil. The red α-helix exhibits the demanding [4, 3, 4, 4]-decomposition. The blue α-helix is the interaction partner for the formation of the coiled coil. (B) Shows a total view on the protein with different colors for its subunits. (C): Amino acid sequence of the coiled-coil range analyzed by the CCdb. (D): Complete sequence of the α-helix. Contact residues of the coiled coil are bold. The contact residues of the [4, 4]-repeat are colored in magenta, corresponding to (A).

Figure 7

PDB-ID 6fjx. (A): Detailed view on the coiled coil. The red α-helix exhibits the demanding [3, 4, 4]-decomposition. The blue α-helix is the interaction partner for the formation of the coiled coil. (B) Shows a total view on the protein with different colors for its subunits. (C): Amino acid sequence of the coiled-coil range analyzed by the CCdb. (D): Complete sequence of the α-helix. Contact residues of the coiled coil are bold. The contact residues of the [4, 4]-repeat are colored in magenta, corresponding to (A).

Figure 8

Input parameters for the CC+ dynamic search interface. Retrieval of any non-redundant dimeric coiled coils.