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Common interruptions in the repeating tripeptide sequence of non-fibrillar collagens: sequence analysis and structural studies on triple-helix peptide models.

ABSTRACT: Interruptions in the repeating (Gly-X1-X2)(n) amino acid sequence pattern are found in the triple-helix domains of all non-fibrillar collagens, and perturbations to the triple-helix at such sites are likely to play a role in collagen higher-order structure and function. This study defines the sequence features and structural consequences of the most common interruption, where one residue is missing from the tripeptide pattern, Gly-X1-X2-Gly-AA(1)-Gly-X1-X2, designated G1G interruptions. Residues found within G1G interruptions are predominantly hydrophobic (70%), followed by a significant amount of charged residues (16%), and the Gly-X1-X2 triplets flanking the interruption are atypical. Studies on peptide models indicate the degree of destabilization is much greater when Pro is in the interruption, GP, than when hydrophobic residues (GF, GY) are present, and a rigid Gly-Pro-Hyp tripeptide adjacent to the interruption leads to greater destabilization than a flexible Gly-Ala-Ala sequence. Modeling based on NMR data indicates the Phe residue within a GF interruption is located on the outside of the triple helix. The G1G interruptions resemble a previously studied collagen interruption GPOGAAVMGPO, designated G4G-type, in that both are destabilizing, but allow continuation of rod-like triple helices and maintenance of the single residue stagger throughout the imperfection, with a loss of axial register of the superhelix on both sides. Both kinds of interruptions result in a highly localized perturbation in hydrogen bonding and dihedral angles, but the hydrophobic residue of a G4G interruption packs near the central axis of the superhelix, while the hydrophobic residue of a G1G interruption is located on the triple-helix surface. The different structural consequences of G1G and G4G interruptions in the repeating tripeptide sequence pattern suggest a physical basis for their differential susceptibility to matrix metalloproteinases in type X collagen.

SUBMITTER: Thiagarajan G

PROVIDER: S-EPMC2738926 | biostudies-other | 2008 Feb

REPOSITORIES: biostudies-other

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Common interruptions in the repeating tripeptide sequence of non-fibrillar collagens: sequence analysis and structural studies on triple-helix peptide models.

Thiagarajan Geetha G Li Yingjie Y Mohs Angela A Strafaci Christopher C Popiel Magdalena M Baum Jean J Brodsky Barbara B

Journal of molecular biology 20071204 3

Interruptions in the repeating (Gly-X1-X2)(n) amino acid sequence pattern are found in the triple-helix domains of all non-fibrillar collagens, and perturbations to the triple-helix at such sites are likely to play a role in collagen higher-order structure and function. This study defines the sequence features and structural consequences of the most common interruption, where one residue is missing from the tripeptide pattern, Gly-X1-X2-Gly-AA(1)-Gly-X1-X2, designated G1G interruptions. Residues ...[more]

PMID: 18187152

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Project description:ObjectiveRecent studies have associated lower urinary tract symptoms (LUTS) in men with prostatic fibrosis, but a definitive link between collagen deposition and LUTS has yet to be demonstrated. The objective of this study was to evaluate ECM and collagen content within normal glandular prostate tissue and glandular BPH, and to evaluate the association of clinical parameters of LUTS with collagen content.MethodsFibrillar collagen and ECM content was assessed in normal prostate (48 patients) and glandular BPH nodules (24 patients) using Masson's trichrome stain and Picrosirius red stain. Second harmonic generation (SHG) imaging was used to evaluate collagen content. Additional BPH tissues (n = 47) were stained with Picrosirius red and the association between clinical parameters of BPH/LUTS and collagen content was assessed.ResultsECM was similar in normal prostate and BPH (p = 0.44). Total collagen content between normal prostate and glandular BPH was similar (p = 0.27), but a significant increase in thicker collagen bundles was observed in BPH (p = 0.045). Using SHG imaging, collagen content in BPH (mean intensity = 62.52; SEM = 2.74) was significantly higher than in normal prostate (51.77±3.49; p = 0.02). Total collagen content was not associated with treatment with finasteride (p = 0.47) or α-blockers (p = 0.52), pre-TURP AUA symptom index (p = 0.90), prostate-specific antigen (p = 0.86), post-void residual (PVR; p = 0.32), prostate size (p = 0.21), or post-TURP PVR (p = 0.51). Collagen content was not associated with patient age in patients with BPH, however as men aged normal prostatic tissue had a decreased proportion of thick collagen bundles.ConclusionsThe proportion of larger bundles of collagen, but not total collagen, is increased in BPH nodules, suggesting that these large fibers may play a role in BPH/LUTS. Total collagen content is independent of clinical parameters of BPH and LUTS. If fibrosis and overall ECM deposition are associated with BPH/LUTS, this relationship likely exists in regions of the prostate other than glandular hyperplasia.

Dataset Information

Common interruptions in the repeating tripeptide sequence of non-fibrillar collagens: sequence analysis and structural studies on triple-helix peptide models.

Publications

Common interruptions in the repeating tripeptide sequence of non-fibrillar collagens: sequence analysis and structural studies on triple-helix peptide models.

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