Environmentally Controlled Curvature of Single Collagen Proteins

Rezaei, Nagmeh; Lyons, Aaron; Forde, Nancy R.

doi:10.1016/j.bpj.2018.09.003

Cited by 47 publications

(65 citation statements)

References 65 publications

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“…It remains unclear just how much of a problem. Indeed, recent statistical analysis of the structure of procollagen obtained from atomic force microscopy shows that the procollagen trimer is more flexible than has been considered previously (Rezaei et al 2018). The persistence length of procollagen trimers exiting the ER remains undefined.…”

Section: Efficient Assembly Of the Copii Coat As A Prerequisite For Pmentioning

confidence: 98%

COPII-dependent ER export in animal cells: adaptation and control for diverse cargo

McCaughey

Stephens

2018

Histochem Cell Biol

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The export of newly synthesized proteins from the endoplasmic reticulum is fundamental to the ongoing maintenance of cell and tissue structure and function. After co-translational translocation into the ER, proteins destined for downstream intracellular compartments or secretion from the cell are sorted and packaged into transport vesicles by the COPII coat protein complex. The fundamental discovery and characterization of the pathway has now been augmented by a greater understanding of the role of COPII in diverse aspects of cell function. We now have a deep understanding of how COPII contributes to the trafficking of diverse cargoes including extracellular matrix molecules, developmental signalling proteins, and key metabolic factors such as lipoproteins. Structural and functional studies have shown that the COPII coat is both highly flexible and subject to multiple modes of regulation. This has led to new discoveries defining roles of COPII in development, autophagy, and tissue organization. Many of these newly emerging features of the canonical COPII pathway are placed in a context of procollagen secretion because of the fundamental interest in how a coat complex that typically generates 80-nm transport vesicles can package a cargo reported to be over 300 nm. Here we review the current understanding of COPII and assess the current consensus on its role in packaging diverse cargo proteins.

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Section: Efficient Assembly Of the Copii Coat As A Prerequisite For Pmentioning

confidence: 98%

COPII-dependent ER export in animal cells: adaptation and control for diverse cargo

McCaughey

Stephens

2018

Histochem Cell Biol

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“…Although imaging in liquid conditions is possible with AFM, here, we deposited the collagen from the specified solution conditions and dried prior to imaging. This follows previous work that used AFM to image and quantify the flexibility of collagen types I, II and III (34,35), to observe interactions between the NC1 domains of collagen IV (36), and to observe binding sites of laminin on collagen IV (37).…”

Section: Atomic Force Microscopy Images Of Collagenmentioning

confidence: 92%

“…2A, along with an image of collagen I for comparison. The acidic conditions preclude lateral assembly of both fibril-forming and collagen IV molecules (27,34), while the presence of chloride ions induces oligomerization of collagen IV protomers, forming networks (13,36). Both proteins possess long chains, representing the collagenous domains.…”

Section: Atomic Force Microscopy Images Of Collagenmentioning

confidence: 99%

Sequence-dependent mechanics of collagen reflect its structural and functional organization

Al-Shaer¹,

Lyons²,

Ishikawa

et al. 2020

Preprint

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Extracellular matrix mechanics influence diverse cellular functions, yet surprisingly little is known about the mechanical properties of their constituent collagens. In particular, network-forming collagen IV, an integral component of basement membranes, has been far less studied than fibril-forming collagens. A key feature differentiating collagen IV is the presence of interruptions in the triple-helix-defining (Gly-X-Y) sequence along its collagenous domain. Here, we used atomic force microscopy (AFM) to determine the impact of these interruptions on the flexibility of collagen. Our extracted flexibility profile reveals that collagen IV possesses highly heterogeneous mechanics, ranging from semi-flexible regions as found for fibril-forming collagens to a lengthy region of high flexibility towards its N terminus. A simple model in which flexibility is dictated only by the presence of interruptions fit the extracted profile reasonably well, providing insight into the alignment of chains and supporting the role of interruptions in instilling flexibility. However, limitations of this model were illuminated by our determination of variable flexibility along continuously triple-helical collagen III, which we found to possess a high-flexibility region around its matrix-metalloprotease (MMP) binding site. Surprisingly, proline content did not correlate with local flexibility in either collagen type. We also found that physiologically relevant changes in pH and chloride concentration did not alter the flexibility of collagen IV, indicating such environmental changes are not used to control its compaction during secretion. Although extracellular chloride ions play a role in triggering collagen IV network formation, they do not appear to modulate the structure of its collagenous domain.

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“…We solved this discrepancy by developing a polymer model that incorporates intrinsic curvature into the WLC, as recently done for collagen fibers 37 . This intrinsically-bent WLC (IBWLC) model has a simple, analytical solution that can be easily fitted to the AFM data, allowing to quantitatively decouple the bending contribution arising from thermal fluctuations (entropic contribution) from that coming from the intrinsic structure of the A-tracts (enthalpic contribution).…”

Section: An Intrinsically-bent Worm-like-chain Model Captures the Lonmentioning

confidence: 99%

“…where we have defined ≡ 1 (2 0 ) ⁄ for convenience. A full derivation of the model can be found in 37 and in Supplemental Material.…”

Section: An Intrinsically-bent Worm-like-chain Model Captures the Lonmentioning

confidence: 99%

Understanding the paradoxical mechanical response of in-phase A-tracts at different force regimes

Marín-González

Pastrana

Bocanegra

et al. 2019

Preprint

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ABSTRACTA-tracts are A:T rich DNA sequences that exhibit unique structural and mechanical properties associated with several functions in vivo. The crystallographic structure of A-tracts has been well characterized. However, their response to forces remains unknown and the variability of their flexibility reported for different length scales has precluded a comprehensive description of the mechanical properties of these molecules. Here, we rationalize the mechanical properties of A-tracts across multiple length scales using a combination of single-molecule experiments and theoretical polymer models applied to DNA sequences present in the C. elegans genome. Atomic Force Microscopy imaging shows that phased A-tracts induce long-range (∼200 nm) bending. Moreover, the enhanced bending originates from an intrinsically bent structure rather than as a consequence of larger flexibility. In support of this, our data were well described with a theoretical model based on the worm-like chain model that includes intrinsic bending. Magnetic tweezers experiments confirm that the observed bent is intrinsic to the sequence and does not rely on particular ionic conditions. Using optical tweezers, we assess the local rigidity of A-tracts at high forces and unravel an unusually stiff character of these sequences, as quantified by their large stretch modulus. Our work rationalizes the complex multiscale flexibility of A-tracts, shedding light on the cryptic character of these sequences.

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Environmentally Controlled Curvature of Single Collagen Proteins

Cited by 47 publications

References 65 publications

COPII-dependent ER export in animal cells: adaptation and control for diverse cargo

COPII-dependent ER export in animal cells: adaptation and control for diverse cargo

Sequence-dependent mechanics of collagen reflect its structural and functional organization

Understanding the paradoxical mechanical response of in-phase A-tracts at different force regimes

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