Structural bases of collagen stabilization induced by proline hydroxylation

Vitagliano, Luigi; Berisio, Rita; Mazzarella, L.; Zagari, Adriana

doi:10.1002/1097-0282(20010415)58:5<459::aid-bip1021>3.0.co;2-v

Cited by 201 publications

(228 citation statements)

References 40 publications

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“…The trans:cis ratio was twofold greater for Ac-Mep-OMe (K trans/cis = 7.4) than for Ac-mepOMe (K trans/cis = 3.6). These data provide an explanation for triple helices formed by (ProMep-Gly) 7 being more stable than those formed by (mep-Pro-Gly) 7 15 . Apparen tly, a balance exists between preorganization of the proper ring pucker and stabilization of a trans peptide bond.…”

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confidence: 73%

“…The self-association of (ProMep-Gly) 7 , (mep-Mep-Gly) 7 , and, to a lesser extent, (mep-Pro-Gly) 7 at 4 °C was confirmed by sedimentation equilibrium experiments. 12 (mep-Pro-Gly) 7 , (Pro-Mep-Gly) 7 , and (mep- …”

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confidence: 76%

“…Mep-Gly) 7 triple helices had T m values of 13, 29, and 36 °C, respectively (Table 1), which are much greater than that of (Pro-Pro-Gly) 7 . Thus, we conclude that steric effects can indeed stabilize the collagen triple helix.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 97%

“…10 A methyl group in this conformation should protrude radially from a collagen triple helix and thus not instill any deleterious interstrand steric interactions. Accordingly, we synthesized mepOH and MepOH 11 and incorporated these nonnatural amino acids into collagen strands to yield: (mep-Pro-Gly) 7 , (Pro-Mep-Gly) 7 , and (mep-Mep-Gly) 7 . We incubated solutions of each strand at ≤4 °C, and then used circular dichroism (CD) spectroscopy to detect formation of triple helices and assess their conformational stability.…”

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confidence: 99%

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Reciprocity of Steric and Stereoelectronic Effects in the Collagen Triple Helix

2006

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Steric and stereoelectronic effects play a defining role in molecular conformation and reactivity. In small molecules, steric and stereoelectronic effects often have dichotomous consequences. For example, the anomeric effect in glycosides yields axial substituents that are disfavored by sterics. 1 Similarly, replacing the steric effect of a methyl group with the stereoelectronic effect of a fluoro group enables a β-peptide to fold. 2 Stereoelectronic effects contribute markedly to the conformational stability of an abundant protein: collagen. 345 Collagen is a fibrous protein comprising a bundle of three parallel strands folded into polyproline type II helices. 6 Each strand consists of ∼300 repeats of the unit: XaaYaa-Gly, where Xaa is often (2S)-proline (Pro) and Yaa is often (2S,4R)-4-hydroxyproline (Hyp). The pyrrolidine ring in the Xaa and Yaa positions have C γ -endo and C γ -exo ring puckers, respectively. 7 These puckers can be preordained by a stereoelectronic effect. Specifically, the gauche effect from a 4S fluoro group stabilizes the C γ -endo pucker; that from a 4R fluoro group stabilizes the C γ -exo pucker (Figure 1). 3 These stereoelectronic effects can marked ly enhance the conformational stability of a collagen triple helix. We reasoned that pyrrolidine ring pucker could instead be fixed and hence collagen stability enhanced by steric rather than stereoelectronic effects. Herein, we report on the bestowal of conformational stability to collagen by steric effects that reiterate stereoelectronic effects.Density functional theory indicated that the pyrrolidine ring of (2S,4R)-4-methylproline (mep) has a strong preference (1.4 kcal/mol) for the C γ -endo pucker and that of (2S,4S)-4-methylproline (Mep) has a strong preference (1.7 kcal/mol) for the C γ -exo pucker ( Figure 1). These conformational preferences are observed in crystalline Ac-mep-NHMe and Ac-MepNHMe, 8 and follow the trend observed in 4-tert-butylprolines. 9 In the preferred conformations, the methyl group of mep and Mep adopts a pseudo-equatorial conformation. 10 A methyl group in this conformation should protrude radially from a collagen triple helix and thus not instill any deleterious interstrand steric interactions. Accordingly, we synthesized mepOH and MepOH 11 and incorporated these nonnatural amino acids into collagen strands to yield: (mep-Pro-Gly) 7 , (Pro-Mep-Gly) 7 , and (mep-Mep-Gly) 7 . We incubated solutions of each strand at ≤4 °C, and then used circular dichroism (CD) spectroscopy to detect formation of triple helices and assess their conformational stability.(mep-Pro-Gly) 7 , (Pro-Mep-Gly) 7 , and (mep-Mep-Gly) 7 formed triple helices at 4 °C, as indicated by an ellipiticity maximum near 225 nm (Figure 2A). The self-association of (ProMep-Gly) 7 , (mep-Mep-Gly) 7 , and, to a lesser extent, (mep-Pro-Gly) 7 at 4 °C was confirmed by sedimentation equilibrium experiments. 12 (mep-Pro-Gly) 7 , (Pro-Mep-Gly) 7 , and (mep- NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMep-Gly) 7 triple helices ha...

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confidence: 73%

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confidence: 76%

Section: Nih-pa Author Manuscriptmentioning

confidence: 97%

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confidence: 99%

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Reciprocity of Steric and Stereoelectronic Effects in the Collagen Triple Helix

2006

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“…The high resolution (1.3 Å) crystallographic structure of (PPG) 10 (Protein Data Bank code 1K6F) revealed accurate φ and ψ angles, and an alignment between chains driven by the charged extremity (N and C terminals) [1]. Based on high resolution structural information of (PPG) 10 [1], generalized as (X-Y-G) 10 , a new hypothesis was proposed for the extra stabilization induced by Hyp in Y [3]. This hypothesis is based on intrinsic conformational propensities of pyrrolidine rings within the triple helix of (X-Y-Gly) 10 .…”

Section: Introductionmentioning

confidence: 99%

Correlation between Raman and X-ray crystallography data of (Pro-Pro-Gly)10

Merlino¹,

Sica²,

Mazzarella³

et al. 2008

Biophysical Chemistry

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Model biopolymers are powerful tools to guide the interpretation of physical properties in complex systems. (Pro-Pro-Gly) 10 , (PPG) 10 , is a collagen model peptide, whose structure is known at high resolution. Herein, Raman microscopy data of (PPG) 10 powders and single crystals are reported. The spectra interpretation leads to an accurate assignment of three well-resolved amide bands corresponding to the three peptide bonds (PP, PG and GP) present in the (PPG) 10 structure.These data together with the availability of torsional angles φ and ψ derived from the highresolution crystal structure, provide the opportunity to test the validity of theoretical equations for the calculation of non canonical amide III bands and represent a reference for theoretical calculations of vibrational spectra and for polyproline II detection in complex proteins.Spectroscopic data do not support the indication of two distinct and equally populated up and down conformations of the pyrrolidin rings observed in the (PPG) 10 crystal structure.

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Crystal structure of a collagen-like polypeptide with repeating sequence Pro-Hyp-Gly at 1.4 � resolution: Implications for collagen hydration

et al. 2000

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The use of polypeptide models has proved to be a valuable tool to obtain accurate information on the collagen triple helix. Here we report the high resolution crystal structure of a collagen‐like polypeptide with repeating sequence Pro–Hyp–Gly. The structure has been refined to an Rfactor of 0.137 and an Rfree of 0.163 using synchrotron diffraction data extending up to 1.4 Å resolution. The polypeptide triple‐helical structure binds a large number of water molecules, in contrast with a previous structure determination at lower resolution. The highly hydrated nature of this polypeptide confirms a number of previous studies conducted both in solution and in the crystal state. In addition, neighboring polypeptide triple helices are directly bound in the crystal through Hyp–Hyp hydrogen‐bonding interactions. This finding supports the idea that Hyp residues may be important for the assembly of the triple helices in the collagen fibrils and may stabilize the fibrils by mediating direct contacts between neighboring molecules. © 2001 John Wiley & Sons, Inc. Biopolymers 56: 8–13, 2001

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Structural bases of collagen stabilization induced by proline hydroxylation

Cited by 201 publications

References 40 publications

Reciprocity of Steric and Stereoelectronic Effects in the Collagen Triple Helix

Reciprocity of Steric and Stereoelectronic Effects in the Collagen Triple Helix

Correlation between Raman and X-ray crystallography data of (Pro-Pro-Gly)10

Crystal structure of a collagen-like polypeptide with repeating sequence Pro-Hyp-Gly at 1.4 � resolution: Implications for collagen hydration

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