Structural Insights into Charge Pair Interactions in Triple Helical Collagen-like Proteins

Fallas, Jorge A.; Dong, Jinhui; Tao, Yizhi Jane; Hartgerink, Jeffrey D.

doi:10.1074/jbc.m111.296574

Cited by 80 publications

(83 citation statements)

References 34 publications

(17 reference statements)

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“…Conversely, Lys-Gly-Asp-type THPs exhibit two axial salt bridges according to results of Hartgerink and co-workers (34). The first bridge has Lys in the i position in the leading chain and Asp in the i ϩ 2 position in the middle chain, whereas the second bridge repeats this pattern between the middle and trailing chains (Fig.…”

Section: Discussionmentioning

confidence: 64%

“…The forces contributing to the lack of stabilization of triple helices by Gly-Asp-Lys and the stabilization of triple helices by Lys-Gly-Asp have been clarified. NMR spectroscopic studies have noted that axial and lateral interactions occur between charged residues with the axial interactions being the most stabilizing (34). Gly-Asp-Lys-type THPs possess two lateral salt bridges that can be formed between residues in the i ϩ 1, i positions in the leading and middle chains and middle and lagging chains (Lys 3 Asp) (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…A salt bridge is not possible between i ϩ 1, i (Lys 3 Asp) in the leading and lagging chains (Fig. 5) as the residues are too far apart (34,36). The lateral Asp 3 Lys interactions expected in the Gly-Asp-Lys THPs evidently stabilize weakly compared with either Gly-ProHyp triplets or Lys-Gly-Asp triplets.…”

Section: Discussionmentioning

confidence: 99%

“…These THPs should also exhibit lateral contact between the lagging chain and the leading chain (34). The lateral interaction shows several possible hydrogen bonds and salt bridges (34). In view of the lower stability of Gly-AspLys THPs and the structural data (34), the lateral interactions probably contribute little to triple-helix stability, and the two axial interactions (i, i ϩ 2) are why Lys-Gly-Asp motifs are stabilizing for triple helices (34).…”

Section: Discussionmentioning

confidence: 99%

“…Arg in the P 2 Ј and P 8 Ј subsites and His in the P 2 Ј and P 4 Ј subsites are favored, but any charged residue in the P 1 Ј subsite is strongly disfavored (17,32,33). THP studies suggest that charged residues regulate the stability of triple-helical structure (34). For example, Gly-Asp-Lys is destabilizing for the triple helix compared with Gly-Pro-Hyp.…”

mentioning

confidence: 99%

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The Role of Collagen Charge Clusters in the Modulation of Matrix Metalloproteinase Activity

Lauer

Bhowmick

Tokmina‐Roszyk

et al. 2014

Journal of Biological Chemistry

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Background:The role of charged clusters in modulating MMP hydrolysis of collagen is unknown. Results: Triple-helical peptides containing charged motifs were as good or better substrates than the parent (non-chargeclustered) peptide. Conclusion: MMP-2 and MMP-9 greatly favored the presence of charged residues. Significance: The lack of Gly-Asp-Lys clusters in native collagens may diminish potential MMP-2 and MMP-9 collagenolytic activity.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

The Role of Collagen Charge Clusters in the Modulation of Matrix Metalloproteinase Activity

Lauer

Bhowmick

Tokmina‐Roszyk

et al. 2014

Journal of Biological Chemistry

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Synthetic Collagen Hydrogels through Symmetric Self‐Assembly of Small Peptides

Tanrikulu,

Dang,

Nelavelli

et al. 2023

Advanced Science

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Animal‐sourced hydrogels, such as collagen, are widely used as extracellular‐matrix (ECM) mimics in tissue engineering but are plagued with problems of reproducibility, immunogenicity, and contamination. Synthetic, chemically defined hydrogels can avoid such issues. Despite the abundance of collagen in the ECM, synthetic collagen hydrogels are extremely rare due to design challenges brought on by the triple‐helical structure of collagen. Sticky‐ended symmetric self‐assembly (SESSA) overcomes these challenges by maximizing interactions between the strands of the triple helix, allowing the assembly of collagen‐mimetic peptides (CMPs) into robust synthetic collagen nanofibers. This optimization, however, also minimizes interfiber contacts. In this work, symmetric association states for the SESSA of short CMPs to probe their increased propensity for interfiber association are modelled. It is found that 33‐residue CMPs not only self‐assemble through sticky ends, but also form hydrogels. These self‐assemblies behave with remarkable consistency across multiple scales and present a clear link between their triple‐helical architecture and the properties of their hydrogels. The results show that SESSA is an effective and robust design methodology that enables the rational design of synthetic collagen hydrogels.

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Empirical estimation of local dielectric constants: Toward atomistic design of collagen mimetic peptides

Pike

Nanda

2015

Biopolymers

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One of the key challenges in modeling protein energetics is the treatment of solvent interactions. This is particularly important in the case of peptides, where much of the molecule is highly exposed to solvent due to its small size. In this study, we develop an empirical method for estimating the local dielectric constant based on an additive model of atomic polarizabilities. Calculated values match reported apparent dielectric constants for a series of Staphylococcus aureus nuclease mutants. Calculated constants are used to determine screening effects on Coulombic interactions and to determine solvation contributions based on a modified Generalized Born model. These terms are incorporated into the protein modeling platform protCAD, and benchmarked on a data set of collagen mimetic peptides for which experimentally determined stabilities are available. Computing local dielectric constants using atomistic protein models and the assumption of additive atomic polarizabilities is a rapid and potentially useful method for improving electrostatics and solvation calculations that can be applied in the computational design of peptides.

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Structural Insights into Charge Pair Interactions in Triple Helical Collagen-like Proteins

Cited by 80 publications

References 34 publications

The Role of Collagen Charge Clusters in the Modulation of Matrix Metalloproteinase Activity

The Role of Collagen Charge Clusters in the Modulation of Matrix Metalloproteinase Activity

Synthetic Collagen Hydrogels through Symmetric Self‐Assembly of Small Peptides

Empirical estimation of local dielectric constants: Toward atomistic design of collagen mimetic peptides

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