Mechanical stability of multidomain proteins and novel mechanical clamps

Sikora, Mateusz; Cieplak, Marek

doi:10.1002/prot.23001

Cited by 34 publications

(41 citation statements)

References 45 publications

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“…The secondary structures of 2EFV consists of four helices (23-32, 41-49, 62-71, 74-86), two 3-10 helices (33-35, 72-73), and two β -strands (12)(13)(14)(15)(16)(17)(54)(55)(56)(57)(58)(59). The knot is of the trefoil type and its ends are located at sites 11 and 73.…”

Section: A 2efvmentioning

confidence: 99%

Structural entanglements in protein complexes

Zhao

Chwastyk

Cieplak

2017

The Journal of Chemical Physics

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We consider multi-chain protein native structures and propose a criterion that determines whether two chains in the system are entangled or not. The criterion is based on the behavior observed by pulling at both temini of each chain simultaneously in the two chains. We have identified about 900 entangled systems in the Protein Data Bank and provided a more detailed analysis for several of them. We argue that entanglement enhances the thermodynamic stability of the system but it may have other functions: burying the hydrophobic residues at the interface, and increasing the DNA or RNA binding area. We also study the folding and stretching properties of the knotted dimeric proteins MJ0366, YibK and bacteriophytochrome. These proteins have been studied theoretically in their monomeric versions so far. The dimers are seen to separate on stretching through the tensile mechanism and the characteristic unraveling force depends on the pulling direction.

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Section: A 2efvmentioning

confidence: 99%

Structural entanglements in protein complexes

Zhao

Chwastyk

Cieplak

2017

The Journal of Chemical Physics

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“…Figure 2 demonstrates that the C-C' pulling of 2B1Y may yield F max close to 1000 pN. This value of the force exceeds F max of about 770 pN predicted by us for the dimeric (3D-domain swapped) cystatin C [21] -for the N-N' pulling at the same speed -in which the shear mechanical clamp is also operational. F max of 2B1Y gets halved for the N-N' pulling and becomes still smaller for N-C and N-C' as then one observes mostly unzipping of the strands as illustrated in figure 3.…”

mentioning

confidence: 67%

Cystine Plug and Other Novel Mechanisms of Large Mechanical Stability in Dimeric Proteins

Sikora

Cieplak

2012

Phys. Rev. Lett.

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We identify three dimeric proteins whose mechanostability is anisotropic and should exceed 1 nN along some directions. They come with distinct mechanical clamps: shear-based, involving a cystine slipknot, and due to dragging of a cystine plug through a cystine ring. The latter two mechanisms are topological in nature and the cystine plug mechanism has not yet been discussed but it turns out to provide the largest resistance to stretching. Its possible applications in elastomers are discussed.

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“…The protein knots identified to date are found within compact globular enzymes (41,42) or within the context of the final assembled form of viral capsids (43)(44)(45). In the case of P1, the stabilizing loop can better be categorized as a type of mechanical clamp in which interdomain contacts play an essential role in stabilizing a knot loop within a multidomain single-chain protein with a patch of H bonds fastening the ends (46,47).…”

Section: Discussionmentioning

confidence: 99%

An intramolecular lock facilitates folding and stabilizes the tertiary structure of Streptococcus mutans adhesin P1

Heim

Crowley²,

Long

et al. 2014

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

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The cariogenic bacterium Streptococcus mutans uses adhesin P1 to adhere to tooth surfaces, extracellular matrix components, and other bacteria. A composite model of P1 based on partial crystal structures revealed an unusual complex architecture in which the protein forms an elongated hybrid alpha/polyproline type II helical stalk by folding back on itself to display a globular head at the apex and a globular C-terminal region at the base. The structure of P1's N terminus and the nature of its critical interaction with the C-terminal region remained unknown, however. We have cocrystallized a stable complex of recombinant N-and C-terminal fragments and here describe a previously unidentified topological fold in which these widely discontinuous domains are intimately associated. The structure reveals that the N terminus forms a stabilizing scaffold by wrapping behind the base of P1's elongated stalk and physically "locking" it into place. The structure is stabilized through a highly favorable ΔG solvation on complex formation, along with extensive hydrogen bonding. We confirm the functional relevance of this intramolecular interaction using differential scanning calorimetry and circular dichroism to show that disruption of the proper spacing of residues 989-1001 impedes folding and diminishes stability of the full-length molecule, including the stalk. Our findings clarify previously unexplained functional and antigenic properties of P1.X-ray crystallography | protein folding | adhesin | Streptococcus | intramolecular lock S treptococcus mutans is a recognized cause of human dental caries (cavities), the most common infectious disease worldwide (1). Identifying how S. mutans interacts with host components at the molecular level is essential to fully understand its virulence properties. The sucrose-independent adhesin P1 (AgI/II, antigen B, PAc) is localized on the surface of this oral pathogen, along with many other streptococci (2-7). In the oral cavity, S. mutans P1 interacts with the salivary agglutinin glycoprotein complex composed predominantly of scavenger receptor gp340/DMBT1 (2, 3, 5-10). Without a complete structural model, the mechanisms by which P1 binds to host components have not yet been fully characterized.P1's primary structure (Fig. 1A) contains a 38-residue signal sequence, the heretofore uncharacterized N-terminal region, three alanine-rich repeats (A1-3), a central domain containing a so-called variable (V) region (11), three proline-rich repeats (P1-3), a C-terminal region consisting of three domains (C1-3), an LPxTG sortase-recognition motif, and wall-and membrane-spanning regions (12, 13). Recent partial X-ray crystal structure and velocity centrifugation studies of the intact protein unveiled a unique architecture in which the ∼185-kDa (1,561-aa) protein folds back on itself to form a ∼50-nm elongated hybrid helical stalk that separates two independent adherence domains, with a globular head at the apex and a globular C-terminal region at the base (13-15) (Fig. 1B).The crystal structure of th...

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Mechanical stability of multidomain proteins and novel mechanical clamps

Cited by 34 publications

References 45 publications

Structural entanglements in protein complexes

Structural entanglements in protein complexes

Cystine Plug and Other Novel Mechanisms of Large Mechanical Stability in Dimeric Proteins

An intramolecular lock facilitates folding and stabilizes the tertiary structure of Streptococcus mutans adhesin P1

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