Interfacial Adsorption and Aggregation Associated Changes in Secondary Structure of Human Calcitonin Monitored by ATR-FTIR Spectroscopy

Hh, Bauer; Müller, Martin; Goette, Jeannette; Hp, Merkle; Up, Fringeli

doi:10.1021/bi00206a034

Cited by 97 publications

(66 citation statements)

References 25 publications

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“…In sarcoplasmic reticulum Ca 2+ -ATPase, the helix position was assigned at 1645 cm -1 . Helical bands in calcinotin were assigned at 1637 cm -1 (43) and in alanin-based peptides as low as 1632-1635 cm -1 (44). In the same spectral region, R-helical bands (additional to bands at the classical position) of apolipoprotein fragments have been proposed (45).…”

Section: Discussionmentioning

confidence: 88%

FTIR-Spectroscopy of Multistranded Coiled Coil Proteins

et al. 1999

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Coiled coils of different order were investigated using infrared (IR) spectroscopy. Recently, we demonstrated that dimeric coiled coils display unique vibrational spectra with at least three separable bands instead of only one band of a classical R-helix in the amide I region.This was attributed to a distortion of the helical structure by the supercoil bending, giving rise to bands that are not observed in the undistorted helix. Here, we investigated coiled coils forming trimers, tetramers, and pentamers. These higher order coiled coils, in general, possess larger superhelical pitches, resulting in a smaller helical distortion. We found that all coiled coils studied, including the native dimeric GCN4 leucine zipper and its variants leading to parallel trimers and tetramers as well as the rod portions of fibritin (parallel trimer), R-actinin (antiparallel spectrin type trimer), and COMP (parallel pentamer), displayed the typical three band pattern of the coiled coil amide I spectra. However, the separation of these three bands and their positional deviation from the classical R-helical band position was correlated to the extent of the helical distortion as reflected by the pitch values of the supercoils. The most pronounced spectral anomaly was found for the tropomyosin dimer with a reported helical pitch of 137 Å, whereas the smallest spectral distortion was found for the pentameric COMP complex and the tetrameric leucine zipper mutant, both with a pitch of about 205 Å.Coiled coils are important oligomerization elements of proteins. They are built from R-helices carrying a sevenresidue repeat pattern (a to g) of hydrophobic and hydrophilic residues in which the hydrophobic residues occupy the first (a) and the fourth (d) positions (1). This generates a hydrophobic seam along the axis of the helix along which two or more helices align laterally in parallel or antiparallel fashion. The tight contact of neighboring helices is achieved by a "knobs into holes" arrangement of the hydrophobic residues in the interface (2). Additional stabilization of the dimer and the correct positioning with respect to register arises from ionic interactions of residues close to the interface. The "classical" form of a coiled coil is doublestranded, parallel, and in register and involves two identical chains. However, there are many other forms of coiled coils. They differ with respect to chain number and orientation and can be homo-as well as heterotypic.The fixed number of two hydrophobic residues in the seven-residue-long repeat unit, (i.e., one hydrophobic residue per 3.5 residues) resulting in an amphiphatic helix versus the slightly higher number of around 3.65 residues per turn of straight R-helix, leads to a left-handed axial shift of the hydrophobic seam around the helix. As a consequence, coiled coils display a distinct left-handed twist. Its pitch length will depend on several factors such as the primary sequence, i.e., the actual choice of hydrophilic and hydrophobic residues within the repeat units. This can res...

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Section: Discussionmentioning

confidence: 88%

FTIR-Spectroscopy of Multistranded Coiled Coil Proteins

et al. 1999

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“…The coiled-coil proteins analyzed in this study (see above) provide an additional example of band shift. Recently, the R-helical band of calcitonin was empirically assigned to 1637 cm -1 (Bauer et al, 1994) and in alanine-based peptides the helical band occurs in the range between 1632 and 1635 cm -1 (Matinez & Milhauser, 1995). One possible explanation for the shift of R-helical bands toward lower wavenumbers could be a distortion in the helices as discussed above.…”

Section: Coiled-coil Proteins Have a Unique Ftir Spectrummentioning

confidence: 99%

Specific Recognition of Coiled Coils by Infrared Spectroscopy: Analysis of the Three Structural Domains of Type III Intermediate Filament Proteins

et al. 1996

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The central domain of cytoplasmic intermediate filament (IF) proteins from vertebrates contains some 310 residues and forms a double-stranded coiled coil (rod) with a length of about 46 nm. The flanking terminal domains show a high cell type specific variability both in sequence and in length. Using Fourier transform infrared (FTIR) spectroscopy we measured secondary structures of isolated domains of type III and IV IF proteins and of the soluble tetramers and the filaments formed by type III IF proteins. The amide I spectrum of the desmin rod is virtually identical to the spectra of other coiled-coil proteins such as tropomyosin and the myosin rod. All these double-stranded coiled coils reveal spectra distinctly different from classical R-helical spectra. The spectrum of coiled coils is a triplet of approximately equally strong bands. One band occurs at normal R-helix position, while the other two are found at lower wavenumbers. Theoretical aspects of these findings are discussed in the accompanying paper by W. C. Reisdorf and S. Krimm [(1996[( ) Biochemistry 35, 1383[( -1386. The amino-terminal head domain of desmin has a multicomponent spectrum with major fractions of -sheet. The carboxy-terminal tail domains of desmin and the neurofilament proteins L and H, the latter in the phosphorylated and in the dephosphorylated forms, have very similar FTIR spectra, indicating mostly random structure. The spectrum of desmin type III protofilaments is very similar to the sum of the spectra of the three isolated domains. Polymerization into filaments seems to induce a small change in secondary structure.

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“…Amyloid fibrils composed of hCT were found to be associated with medullary carcinoma of the thyroid (17)(18)(19). It was also found that synthetic hCT can form amyloid fibrils in vitro with a similar morphology to the deposits found in the thyroid (17)(18)(19)(20)(21)(22)(23). The in vitro process of amyloid formation is affected by the pH of the medium (23).…”

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confidence: 99%

“…However, studies of hCT fibrils using circular dichroism, fluorescence, and infrared spectroscopy revealed that fibrillated hCT molecules have both ␣-helical and ␤-sheet secondary structure components (21). NMR spectroscopy studies have shown that in various structure-promoting solvents like trifluoroethanol/H 2 O, hCT adopts an amphiphilic ␣-helical conformation predominantly in the residue range of 8 -22 (24 -25).…”

mentioning

confidence: 99%

Amyloid Fibril Formation by Pentapeptide and Tetrapeptide Fragments of Human Calcitonin

Reches

Porat

Gazit

2002

Journal of Biological Chemistry

329

321

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The process of amyloid fibril formation by the human calcitonin hormone is associated with medullary thyroid carcinoma. Based on the effect of pH on the fibrillization of human calcitonin, the analysis of conformationally constrained analogues of the hormone, and our suggestion regarding the role of aromatic residues in the process of amyloid fibril formation, we studied the ability of a short aromatic charged peptide fragment of calcitonin (NH 2 -DFNKF-COOH) to form amyloid fibrils. Here, using structural and biophysical analysis, we clearly demonstrate the ability of this short peptide to form well ordered amyloid fibrils. A shorter truncated tetrapeptide, NH 2 -DFNK-COOH, also formed fibrils albeit less ordered than those formed by the pentapeptide. We could not detect amyloid fibril formation by the NH 2 -FNKF-COOH tetrapeptide, the NH 2 -DFN-COOH tripeptide, or the NH 2 -DANKA-COOH phenylalanine to the alanine analogue of the pentapeptide. The formation of amyloid fibrils by rather hydrophilic peptides is quite striking, because it was speculated that hydrophobic interactions might play a key role in amyloid formation. This is the first reported case of fibril formation by a peptide as short as a tetrapeptide and one of very few cases of amyloid formation by pentapeptides. Because the aromatic nature seems to be the only common property of the various very short amyloid-forming peptides, it further supports our hypothesis on the role of aromatic interactions in the process of amyloid fibril formation.The process of amyloid fibril formation is associated with a large number of diseases of unrelated origin. A partial list includes Alzheimer's disease, Parkinson's disease, Type II diabetes, Prion diseases, Familial British dementia, and several familial amyloidosises (1-7). All of these diseases are characterized by the transformation of soluble proteins into aggregated fibrillar deposits in different organs and tissues. The pathological significance of amyloid fibril formation is not completely understood in all cases. One such example is aortic medial amyloid deposits that occur virtually in all individuals older than 60 years, but its medical consequence is not known yet (8).Although different amyloid-forming proteins do not share clear sequence homology, the fibrillar structures that are being formed have very similar physicochemical and ultrastructural characteristics as determined by transmission electron microscopy x-ray fiber diffraction, and other biophysical techniques (1-7). Furthermore, amyloid fibrils are being formed in vitro also by disease-unrelated proteins (9 -13). This finding suggests that amyloid fibrils may serve as a generic structural form of aggregated proteins (1-7). Nevertheless, despite the significant medical importance of the amyloid fibril formation process and its consideration as a universal structural form, the exact mechanism that leads to the self-assembly of polypeptides into ordered fibrils is not fully understood.Human calcitonin (hCT) 1 is a 32-amino acid polypeptide hor...

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Interfacial Adsorption and Aggregation Associated Changes in Secondary Structure of Human Calcitonin Monitored by ATR-FTIR Spectroscopy

Cited by 97 publications

References 25 publications

FTIR-Spectroscopy of Multistranded Coiled Coil Proteins

FTIR-Spectroscopy of Multistranded Coiled Coil Proteins

Specific Recognition of Coiled Coils by Infrared Spectroscopy: Analysis of the Three Structural Domains of Type III Intermediate Filament Proteins

Amyloid Fibril Formation by Pentapeptide and Tetrapeptide Fragments of Human Calcitonin

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