Parallels between DNA and collagen - comparing elastic models of the double and triple helix

Abstract

Multi-stranded helices are widespread in nature. The interplay of polymeric properties with biological function is seldom discussed. This study probes analogies between structural and mechanical properties of collagen and DNA. We modeled collagen with Eulerian rotational and translational parameters of adjacent rungs in the triple-helix ladder and developed statistical potentials by extracting the dispersion of the parameters from a database of atomic-resolution structures. The resulting elastic model provides a common quantitative way to describe collagen deformations upon interacting with integrins or matrix metalloproteinase and DNA deformations upon protein binding. On a larger scale, deformations in Type I collagen vary with a periodicity consistent with the D-periodic banding of higher-order fibers assemblies. This indicates that morphologies of natural higher-order collagen packing might be rooted in the characteristic deformation patterns.

Figure 1

Defining geometric parameters of a collagen triple helical step. (a) The reference frame of a Cα triangle (see Methods for details). (b) The middle reference frame between successive triangles of a triple helical step. (c) Illustration of positive values of the six step parameters. Triangles are obtained with procedures in the 3DNA software package.

Figure 2

Stacking models of (a) GP₂-GP₂, and (b) GP₀-GP₀ steps built from their mean step values, where the subscripts are the numbers of imino (Pro/Hyp) residues in a Gly/X/Y triad. The edges of the triangles connecting the two Cα atoms of non-Gly residues are shaded in black.

Figure 3

Derived energy contours of (a) Slide-Shift, (b) Rise-Shift, (c) Roll-Tilt, and (d) Twist-Tilt with high (GP₂-GP₂), middle (GP_x-GP_y, x < 2 or y < 2), and low (GP₀-GP₀) imino contents. The level of the elliptical equi-potential contours corresponds to three times the root-mean square deviation (3σ) of the data points.

Figure 4

(a) Shift, (b) Rise, (c) Twist, (d) deformation scores of integrin-bound complexes (PDB: 1DZI, 4BJ3) and integrin-free (DPB: 1Q7D) triple helices with the same sequence^,,. The mean step parameter values, or ‘equilibrium states’ are listed in Table S3. The integrin-bound region is shaded in grey. The sequences are aligned by step number. The Phe and Hyp residues contacted by integrin Asn154 and Leu296 are framed by color-coded rectangles: black for the 1:1 complex; green for integrin molecule A; light blue for integrin molecule B (contact only to Phe).

Figure 5

Deformed triple helices in integrin-collagen complexes and double helices in a protein-DNA complex. The deformation scores are color-coded and mapped on ribbon representations of collagen in the (a) 1:1 and (b) 2:1 integrin-collagen complexes (PDB ID: 1DZI, 4BJ3)^,. The same integrin residues, Asn154 and Leu296, contact Phe and Hyp in the various chains of the triple helices. Contacting pairs are shown in ball-and-sticks. The Glu residues involved in the three metal ion-dependent adhesion sites (MIDAS) are also shown in ball-and-stick representations. (c) Corresponding deformation scores and images of the TATA-box DNA-protein complex (PDB ID: 1YTB). See supplement for calculation of DNA deformation scores.

Figure 6

(a) Shift, (b) Slide, (c) Twist, (e) deformation scores of two states of matrix metalloproteinase 1(MMP1)-bound triple helices (PDB: 4AUO). The mean step parameter values, or ‘equilibrium states’, are listed in Table S3. The sequences contacted (atom-atom distance ≤ 4 Å) by MMP1 N-terminal catalytic (Cat) and C-terminal hemopexin (Hpx) domains are shaded in light cyan and grey, respectively. The sequences are aligned along the step number.

Figure 7

Collagen and DNA deformations induced by the indirect contacts of ligands. The deformation scores are color-coded and mapped on two states of the triple helices, (a) and (b), in the MMP-collagen complexes (PDB ID: 4AUO), and (c) the HPV E2 protein-DNA complex (PDB ID: 1JJ4).

Figure 8

Highly deformed steps in natural collagen models and the fluctuation frequencies of the deformation scores found upon Fourier transformation. (a) Top left: a schematic representation of triple helix packing in the Type I collagen microfibril. Top right: an enlarged view of the in situ packing model. Bottom: an individual triple helix in the fibril. The 11 highly deformed steps (deformation scores ≥ 3000) highlighted with magenta spheres in the packing model and the individual triple helix. (b) The deformation scores are plotted against collagen sequence number. (c) Fluctuation frequency peaks of deformation scores are derived from Fourier transformation. The most significant frequency is 4, and the corresponding periodicity is 252 residues (periodicity = 1008 residues/frequency).