How Sequence Determines Elasticity of Disordered Proteins

Cheng, Shanmei; Çetinkaya, Murat; Gräter, Frauke

doi:10.1016/j.bpj.2010.10.011

Cited by 68 publications

(67 citation statements)

References 37 publications

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“…As a consequence, the end-to-end C-C distance for each glycine is more sensitive to force, and thus more flexible. Similar observations were made for short protein fragments whose flexibility is sensitive to the glycine content (25). To confirm this particular behavior, we performed simulations of an all-glycine analog of ubiquitin, i.e., a protein containing the same number of residues but all mutated to glycine.…”

supporting

confidence: 59%

Elasticity, structure, and relaxation of extended proteins under force

Stirnemann¹,

Giganti

Fernández

et al. 2013

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

110

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Force spectroscopies have emerged as a powerful and unprecedented tool to study and manipulate biomolecules directly at a molecular level. Usually, protein and DNA behavior under force is described within the framework of the worm-like chain (WLC) model for polymer elasticity. Although it has been surprisingly successful for the interpretation of experimental data, especially at high forces, the WLC model lacks structural and dynamical molecular details associated with protein relaxation under force that are key to the understanding of how force affects protein flexibility and reactivity. We use molecular dynamics simulations of ubiquitin to provide a deeper understanding of protein relaxation under force. We find that the WLC model successfully describes the simulations of ubiquitin, especially at higher forces, and we show how protein flexibility and persistence length, probed in the force regime of the experiments, are related to how specific classes of backbone dihedral angles respond to applied force. Although the WLC model is an average, backbone model, we show how the protein side chains affect the persistence length. Finally, we find that the diffusion coefficient of the protein's end-to-end distance is on the order of 10 8 nm 2 /s, is position and side-chain dependent, but is independent of the length and independent of the applied force, in contrast with other descriptions.internal diffusion | potential of mean force | protein elasticity T he development of single-molecule force spectroscopies [atomic force microscopy (AFM), and optical or magnetic tweezers] in the last two decades has opened a whole new and exciting field (1, 2). It is now possible to manipulate biomolecules directly at a molecular level and to study their behavior under force (3). It is therefore not surprising that these techniques have been applied in a broad gamut of contexts, in particular for proteins. In some cases, including enzyme catalysis (4), protein-ligand interaction (5), or folding and unfolding events (6), force is used as a probe, altering the free-energy landscape and the dynamics of the protein (7), and provides valuable kinetic and mechanistic insights. For other systems, force is of direct biological relevance [e.g., cellular adhesion (8) or muscle elasticity (9)].The elasticity of a polypeptide is typically modeled using the worm-like chain (WLC) (1, 2) model of polymer elasticity. Although this simple model from polymer physics has proven remarkably successful at describing and interpreting experimental data, it lacks molecular details associated with proteins extended under force. However, substrate flexibility to adopt the right geometry is key in many situations, including, e.g., molecular recognition (10) or enzymatic reactivity (11). Therefore, a precise understanding of how force modulates and influences protein flexibility at a single-amino acid level is essential and is not provided by the aforementioned model.From a dynamical perspective, it is still unclear how applied force affects internal diffusion ...

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supporting

confidence: 59%

Elasticity, structure, and relaxation of extended proteins under force

Stirnemann¹,

Giganti

Fernández

et al. 2013

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

110

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“…In line with these observations, mutating proline residues in a short, disordered elastin-like peptide has been shown to induce a stepwise expansion 112 . In contrast, the overall stiffness of four disordered peptides were reported to be more correlated with their PPII contents than their proline counts, whereas the intrinsic capacities for hairpin structures strongly correlated with the numbers of glycines and prolines 113 . Therefore, the possible role(s) of prolines in compacting, or expanding IDPs conformations would depend on the context.…”

Section: Prolines In Idps/idprs: Structural and Functional Rolesmentioning

confidence: 69%

The alphabet of intrinsic disorder

Theillet¹,

Kalmár

Tompa

et al. 2013

Intrinsically Disordered Proteins

237

145

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A significant fraction of every proteome is occupied by biologically active proteins that do not form unique three-dimensional structures. These intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) have essential biological functions and are characterized by extensive structural plasticity. Such structural and functional behavior is encoded in the amino acid sequences of IDPs/IDPRs, which are enriched in disorder-promoting residues and depleted in order-promoting residues. In fact, amino acid residues can be arranged according to their disorder-promoting tendency to form an alphabet of intrinsic disorder that defines the structural complexity and diversity of IDPs/IDPRs. This review is the first in a series of publications dedicated to the roles that different amino acid residues play in defining the phenomenon of protein intrinsic disorder. We start with proline because data suggests that of the 20 common amino acid residues, this one is the most disorder-promoting.

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“…Each EPYC1 is represented by 3, 4, or 5 connected binding sites: the binding sites are spheres of radius R E = 0.9 nm, which is the radius of a compact region of 18 amino acids representing the repeat region of EPYC1. We model the unstructured chain of 34 amino acids separating these repeats as harmonic springs with zero rest length and stiffness 0.24 k B T /nm 2 , reflecting the entropic elasticity of a worm-like polymer chain consisting of 34 units of size 0.35 nm (the approximate size of an amino acid) with a persistence length of 0.5 nm (a rough consensus for polypeptide chains [Hofmann et al , 2012, Cheng et al ., 2010]).…”

Section: Methodsmentioning

confidence: 99%

The Eukaryotic CO2-Concentrating Organelle Is Liquid-like and Exhibits Dynamic Reorganization

Rosenzweig

Cuellar

et al. 2017

Cell

343

335

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Summary Approximately 30–40% of global CO2 fixation occurs inside a non-membrane-bound organelle called the pyrenoid, which is found within the chloroplasts of most eukaryotic algae. The pyrenoid matrix is densely packed with the CO2-fixing enzyme Rubisco, and is thought to be a crystalline or amorphous solid. Here, we show that the pyrenoid matrix of the unicellular alga Chlamydomonas reinhardtii is not crystalline, but behaves as a liquid that dissolves and condenses during cell division. Furthermore, we show that new pyrenoids are formed both by fission and de novo assembly. Our modeling predicts the existence of a “magic number” effect associated with special, highly stable heterocomplexes that influences phase separation in liquid-like organelles. This view of the pyrenoid matrix as a phase-separated compartment provides a paradigm for understanding its structure, biogenesis, and regulation. More broadly, our findings expand our understanding of the principles that govern the architecture and inheritance of liquid-like organelles.

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How Sequence Determines Elasticity of Disordered Proteins

Cited by 68 publications

References 37 publications

Elasticity, structure, and relaxation of extended proteins under force

Elasticity, structure, and relaxation of extended proteins under force

The alphabet of intrinsic disorder

The Eukaryotic CO2-Concentrating Organelle Is Liquid-like and Exhibits Dynamic Reorganization

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