The Polypeptide Chain Configuration of Collagen

Cowan, P.; McGavin, Stewart; North, A. C. T.

doi:10.1038/1761062a0

Cited by 206 publications

(75 citation statements)

References 18 publications

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“…5B) places amyloid among the most rigid proteinaceous materials in nature (6,25), with a stiffness comparable to that of dragline spider silk (1-10 GPa) (12) and collagen fibers (∼1 GPa) (26). This is intriguing, as the cross-β structure of amyloid shares many similarities with the crystalline regions of spider silk (27) and the triple helix of collagen (28) in that each of these materials consists of a network of intermolecular hydrogen bonds (Fig. 5A).…”

Section: Resultsmentioning

confidence: 85%

Exceptional rigidity and biomechanics of amyloid revealed by 4D electron microscopy

Fitzpatrick

Park

Zewail

2013

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

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Amyloid is an important class of proteinaceous material because of its close association with protein misfolding disorders such as Alzheimer's disease and type II diabetes. Although the degree of stiffness of amyloid is critical to the understanding of its pathological and biological functions, current estimates of the rigidity of these β-sheet-rich protein aggregates range from soft (10 8 Pa) to hard (10 10 Pa) depending on the method used. Here, we use timeresolved 4D EM to directly and noninvasively measure the oscillatory dynamics of freestanding, self-supporting amyloid beams and their rigidity. The dynamics of a single structure, not an ensemble, were visualized in space and time by imaging in the microscope an amyloid-dye cocrystal that, upon excitation, converts light into mechanical work. From the oscillatory motion, together with tomographic reconstructions of three studied amyloid beams, we determined the Young modulus of these highly ordered, hydrogenbonded β-sheet structures. We find that amyloid materials are very stiff (10 9 Pa). The potential biological relevance of the deposition of such a highly rigid biomaterial in vivo are discussed.cross-β structure | nanomechanics | microcantilever A myloid fibrils are filamentous polypeptide aggregates whose intra-and extracellular deposition is associated with more than 50 human disorders ranging from Alzheimer's disease to type II diabetes (1, 2). Normally soluble peptides or proteins with a wide range of amino acid sequences can aggregate into amyloid fibrils with a characteristic "cross-β" core structure composed of arrays of β-sheets running parallel to the long axis of the fibrils (3, 4). It is thought that this universal cross-β structure is responsible for the persistence and stability of these obdurate aggregates as a result of the long-range order of its hydrogenbonded β-sheets (5-7). However, indirect ensemble measurements of the stiffness, or Young modulus (Y), of amyloid by statistical analysis of fluctuations in fibril shape have resulted in conflicting results, ranging from highly flexible [Y range of 90-320 MPa (8)] to extremely stiff [Y range of 2-14 GPa (6)]. More direct methods such as atomic force microscopy (AFM) nanoindentation, in which an AFM tip directly presses on an individual fibril to measure the contact stiffness, display an equally large Y range; results vary, e.g., for insulin fibrils, from 5 to 50 MPa (9) in one study and from 3 to 4 GPa (10) in another study.The difference in Y of more than three orders of magnitude presents a serious question: is amyloid highly flexible like elastin [Y = 1.1 MPa (11)] or is it rigid like spider dragline silk [Y range of 1-10 GPa (12)]? To answer this important question, we measured Y values of amyloid "single particles" directly by visualizing in space and time the oscillations of three individual "amyloid beams" composed of the universal cross-β structure by using time-resolved 4D EM (13,14). Results and DiscussionTime-Resolved Dynamics of the Cross-β Steric Zipper. The concept is as fol...

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Section: Resultsmentioning

confidence: 85%

Exceptional rigidity and biomechanics of amyloid revealed by 4D electron microscopy

Fitzpatrick

Park

Zewail

2013

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

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“…In the 1950s, elucidation of the structural features of polyproline 1 and polyglycine 2 provided a conceptual framework for the proposal of the triple-helical structure of collagen and insight into its basic stabilizing interactions. The collagen triplehelix structure, as proposed by Ramachandran and Kartha (1955), 3 Rich and Crick (1955), 4 and Cowan et al (1955), 5 consists of three polypeptide chains, each in a polyproline II-like (PPII) conformation, supercoiled around a common axis. The triple-helix is stabilized by its high content of proline and Triple-Helical Peptides: An Approach to Collagen Conformation, Stability, and Self-Association This article is dedicated to the memory of Elkan Blout, who was the Ph.D. advisor of B.B.…”

Section: Introductionmentioning

confidence: 99%

Triple‐helical peptides: An approach to collagen conformation, stability, and self‐association

et al. 2008

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Peptides have been an integral part of the collagen triple‐helix structure story, and have continued to serve as useful models for biophysical studies and for establishing biologically important sequence‐structure‐function relationships. High resolution structures of triple‐helical peptides have confirmed the basic Ramachandran triple‐helix model and provided new insights into the hydration, hydrogen bonding, and sequence dependent helical parameters in collagen. The dependence of collagen triple‐helix stability on the residues in its (Gly‐X‐Y)n repeating sequence has been investigated by measuring melting temperatures of host‐guest peptides and an on‐line collagen stability calculator is now available. Although the presence of Gly as every third residue is essential for an undistorted structure, interruptions in the repeating (Gly‐X‐Y)n amino acid sequence pattern are found in the triple‐helical domains of all nonfibrillar collagens, and are likely to play a role in collagen binding and degradation. Peptide models indicate that small interruptions can be incorporated into a rod‐like triple‐helix with a highly localized effect, which perturbs hydrogen bonds and places the standard triple‐helices on both ends out of register. In contrast to natural interruptions, missense mutations which replace one Gly in a triple‐helix domain by a larger residue have pathological consequences, and studies on peptides containing such Gly substitutions clarify their effect on conformation, stability, and folding. Recent studies suggest peptides may also be useful in defining the basic principles of collagen self‐association to the supramolecular structures found in tissues. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 345–353, 2008.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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“…The Polyproline II (PII) helices correspond to a specific local fold first discovered in fibrous proteins [144][145][146]. They contribute to the creation of coiled coil supersecondary structures characteristic of these fibrous proteins but are also found in numerous globular proteins.…”

Section: Secondary Structuresmentioning

confidence: 99%

Local Protein Structures

Offmann¹,

Tyagi²,

Brevern

2007

CBIO

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Protein structures are classically described as composed of two regular states, the α-helices and the β-strands and one non-regular and variable state, the coil. Nonetheless, this simple definition of secondary structures hides numerous limitations. In fact, the rules for secondary structure assignment are complex. Thus, numerous assignment methods based on different criteria have emerged leading to heterogeneous and diverging results. In the same way, 3 states may over-simplify the description of protein structure; 50% of all residues, i.e., the coil, are not genuinely described even when it encompass precise local protein structures.Description of local protein structures have hence focused on the elaboration of complete sets of small prototypes or "structural alphabets", able to analyze local protein structures and to approximate every part of the protein backbone. They have also been used to predict the protein backbone conformation and in ab initio / de novo methods. In this paper, we review different approaches towards the description of local structures, mainly through their description in terms of secondary structures and in terms of structural alphabets. We provide some insights into their potential applications.

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The Polypeptide Chain Configuration of Collagen

Cited by 206 publications

References 18 publications

Exceptional rigidity and biomechanics of amyloid revealed by 4D electron microscopy

Exceptional rigidity and biomechanics of amyloid revealed by 4D electron microscopy

Triple‐helical peptides: An approach to collagen conformation, stability, and self‐association

Local Protein Structures

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