Gly-Pro-Arg Confers Stability Similar to Gly-Pro-Hyp in the Collagen Triple-helix of Host-Guest Peptides

Yang, Wei; Chan, Virginia C.; Kirkpatrick, Alan; Ramshaw, John A. M.; Brodsky, Barbara

doi:10.1074/jbc.272.46.28837

Cited by 99 publications

(88 citation statements)

References 24 publications

(34 reference statements)

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“…1). The host peptide GPO (19) as well as peptides GSO and GPS showed values of [⍜] 225 Ϸ 4,000 deg⅐cm 2 ⅐dmol Ϫ1 in native conditions, indicating a fully triple-helical conformation, as also found for other related host-guest peptides (19)(20)(21)(22)27). The corresponding values for peptides APO (3,600 deg⅐cm 2 ⅐dmol Ϫ1 ), CPO under oxidizing conditions (3,200 deg⅐cm 2 ⅐dmol Ϫ1 ), and SPO (3,200 deg⅐cm 2 ⅐dmol Ϫ1 ) are lower but are still in the range expected for a triple helix, whereas the CD amplitudes of peptides CPO red (1,600 deg⅐cm 2 ⅐dmol Ϫ1 ), DPO (2,000 deg⅐cm 2 ⅐dmol Ϫ1 ), EPO (1,700 deg⅐cm 2 ⅐dmol Ϫ1 ), RPO (1,600 deg⅐cm 2 ⅐dmol Ϫ1 ), and VPO (1,300 deg⅐cm 2 ⅐dmol Ϫ1 ) are comparable with the CD amplitude of a single-chain polyproline II helix (24,28,29).…”

Section: Resultsmentioning

confidence: 94%

“…This design embeds a guest triplet Gly-Xaa-Yaa near the middle of a Gly-Pro-Hyp-rich environment and has an acetylated N terminus and amidated C terminus to eliminate interactions between guest triplets and ionized ends (25,26). The host peptide acetyl-(Gly-Pro-Hyp) 8 -Gly-Gly-amide has a T m ϭ 45°C, and all of the more than 40 peptides with different L-amino acids in the Xaa and Yaa positions studied thus far formed stable triple helices with melting temperatures in the 20-45°C range (19)(20)(21)(22)27). For this study, the Gly residue in the guest triplet is replaced by another residue, Zaa, with Xaa and Yaa being Pro and Hyp, respectively, yielding a guest triplet Zaa-Pro-Hyp.…”

Section: Resultsmentioning

confidence: 99%

“…Peptides were synthesized by using fluorenylmethoxycarbonyl chemistry, purified, and identified by mass spectrometry as described (19)(20)(21)(22).…”

Section: Methodsmentioning

confidence: 99%

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Destabilization of osteogenesis imperfecta collagen-like model peptides correlates with the identity of the residue replacing glycine

Beck

Chan

Shenoy

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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179

198

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Mutations resulting in replacement of one obligate Gly residue within the repeating (Gly-Xaa-Yaa) n triplet pattern of the collagen type I triple helix are the major cause of osteogenesis imperfecta (OI). Phenotypes of OI involve fragile bones and range from mild to perinatal lethal. In this study, host-guest triple-helical peptides of the form acetyl-(Gly-Pro-Hyp) 3-Zaa-Pro-Hyp-(Gly-Pro-Hyp)4-GlyGly-amide are used to isolate the influence of the residue replacing Gly on triple-helix stability, with Zaa ‫؍‬ Gly, Ala, Arg, Asp, Glu, Cys, Ser, or Val. Any substitution for Zaa ‫؍‬ Gly (melting temperature, Tm ‫؍‬ 45°C) results in a dramatic destabilization of the triple helix. For Ala and Ser, T m decreases to Ϸ10°C, and for the Arg-, Val-, Glu-, and Asp-containing peptides, Tm < 0°C. A Gly 3 Cys replacement results in T m < 0°C under reducing conditions but shows a broad transition (T m Ϸ 19°C) in an oxidizing environment. Addition of trimethylamine N-oxide increases T m by Ϸ5°C per 1 M trimethylamine N-oxide, resulting in stable triple-helix formation for all peptides and allowing comparison of relative stabilities. The order of disruption of different Gly replacements in these peptides can be represented as Ala < Ser < CPOred < Arg < Val < Glu < Asp. The rank of destabilization of substitutions for Gly in these Gly-ProHyp-rich homotrimeric peptides shows a significant correlation with the severity of natural OI mutations in the ␣1 chain of type I collagen.

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Destabilization of osteogenesis imperfecta collagen-like model peptides correlates with the identity of the residue replacing glycine

Beck

Chan

Shenoy

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

179

198

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“…Arginine or lysine residues located in the Xaa position as well as lysines in the Yaa position of Gly-Xaa-Yaa triplets were substituted by alanines, whereas proline was used to replace arginines in the Yaa position. Previous studies show arginine and proline in the Yaa position to be equally stabilizing, whereas the stability of arginine in the Xaa position as well of lysines in both positions were equivalent to alanine (22).…”

Section: Contribution Of Individual Basic Residues To Heparinmentioning

confidence: 99%

“…However, in each HBD we found the most important residue to be a lysine. This could be a particularity of collagen, where arginines in Yaa position play an important role in the stability of the triple-helical structure (22). Molecular modeling studies show that arginines can form hydrogen bonds with the backbone of the same or the neighboring polypeptide chains (32).…”

Section: Heparin-binding Capacity Of Colq Resides Exclusively In the mentioning

confidence: 99%

Two Different Heparin-binding Domains in the Triple-helical Domain of ColQ, the Collagen Tail Subunit of Synaptic Acetylcholinesterase

Deprez

Inestrosa

Krejci

2003

Journal of Biological Chemistry

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ColQ, the collagen tail subunit of asymmetric acetylcholinesterase, is responsible for anchoring the enzyme at the vertebrate synaptic basal lamina by interacting with heparan sulfate proteoglycans. To get insights about this function, the interaction of ColQ with heparin was analyzed. For this, heparin affinity chromatography of the complete oligomeric enzyme carrying different mutations in ColQ was performed. Results demonstrate that only the two predicted heparin-binding domains present in the collagen domain of ColQ are responsible for heparin interaction. Despite their similarity in basic charge distribution, each heparin-binding domain had different affinity for heparin. This difference is not solely determined by the number or nature of the basic residues conforming each site, but rather depends critically on local structural features of the triple helix, which can be influenced even by distant regions within ColQ. Thus, ColQ possesses two heparinbinding domains with different properties that may have non-redundant functions. We hypothesize that these binding sites coordinate acetylcholinesterase positioning within the organized architecture of the neuromuscular junction basal lamina.At vertebrate cholinergic synapses, acetylcholinesterase (AChE) 1 rapidly hydrolyzes the neurotransmitter acetylcholine, thereby terminating synaptic transmission. This key function does not only require a high catalytic turnover number but also a strategic positioning of the enzyme. This is achieved by the association of AChE catalytic subunits with structural subunits that bring them to the site of action. In the case of asymmetric AChE, the collagen ColQ is responsible for the localization of the enzyme at the vertebrate neuromuscular junction. Inactivation of the ColQ gene in mice or mutations in the human ColQ gene result in the absence of enzyme accumulation at the neuromuscular junction and are the cause of a congenital myasthenic syndrome (type 1c) (1, 2).As found in other collagens, ColQ contains a central triplehelical domain surrounded by non-collagenous N-and C-terminal domains (Fig. 1A). Each N-terminal domain organizes an AChE tetramer, so the triple-helical structure generates an A 12 or asymmetric AChE form with 12 catalytic subunits (3, 4). The collagen domain is characterized by Gly-Xaa-Yaa repeats and a high proportion of the stabilizing proline and hydroxyproline residues. The C-terminal domain is divided into a proline-rich region, important for triple-helix formation (5), and a cysteinerich region probably involved in the anchorage of AChE at the neuromuscular junction, since mutations in this region prevent the accumulation of AChE in congenital myasthenic syndrome type 1c patients (2).Heparan sulfate proteoglycans (HSPGs) have been implicated in the anchorage of asymmetric AChE to the synaptic basal lamina by interacting with ColQ through their heparan sulfate (HS) chains. This was proposed after showing that AChE could be specifically solubilized from the tissue with heparinase as well as with HS and ...

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Structural consequences ofD-amino acids in collagen triple-helical peptides

Shah¹,

Brodsky²,

Kirkpatrick

et al. 1999

Biopolymers

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Gly-Pro-Arg Confers Stability Similar to Gly-Pro-Hyp in the Collagen Triple-helix of Host-Guest Peptides

Cited by 99 publications

References 24 publications

Destabilization of osteogenesis imperfecta collagen-like model peptides correlates with the identity of the residue replacing glycine

Destabilization of osteogenesis imperfecta collagen-like model peptides correlates with the identity of the residue replacing glycine

Two Different Heparin-binding Domains in the Triple-helical Domain of ColQ, the Collagen Tail Subunit of Synaptic Acetylcholinesterase

Structural consequences ofD-amino acids in collagen triple-helical peptides

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