Appendant structure plays an important role in amyloidogenic cystatin dimerization prior to domain swapping

Yu, Yuanyuan; Liu, Xin; He, Jing; Zhang, Mengyuan; Li, Hui; Wei, Dong‐Qing; Song, Yue

doi:10.1080/07391102.2012.674282

Cited by 6 publications

(8 citation statements)

References 30 publications

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“…As previously reported, the classic amyloidogenic mutant I66Q displays an obvious RMSD fluctuation compared to WT (Fig. 2), and this is considered to be a characteristic that promotes amyloid fibrillization (Yu et al, 2012). Interestingly, the RMSD of I66Q and W increased dramatically as soon as the simulation began.…”

Section: Resultssupporting

confidence: 76%

“…It has been demonstrated that in MD simulations, high temperature and low pH value can accelerate protein unfolding without changing the pathway of the 9 unfolding process (Day, Bennion, Ham, & Daggett, 2002). Therefore, we performed the simulations under the same extreme conditions (330 K (57 °C) and pH 2) as those used in our previous experiments (He et al, 2005;Yu et al, 2012;Yu et al, 2010), which allow the system to reach the equilibrated regions in minimum simulation time and with minimum computational expense. The RMSD value reached a relative equilibrium region in 10 ns in all simulations (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…1A). In our previous work, we have demonstrated that AS plays an important role in amyloidogenic cystatin dimerization between two cystatin monomers (Yu et al, 2012). Alignment of HCC and cC showed that E82 of cC corresponds to P84 of HCC ( Fig.…”

Section: Introductionmentioning

confidence: 83%

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Is the absence of alpha-helix 2 in the appendant structure region the major contributor to structural instability of human cystatin C?

Zhou

Qin

et al. 2019

Journal of Biomolecular Structure and Dynamics

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Section: Resultssupporting

confidence: 76%

Section: Resultsmentioning

confidence: 99%

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Is the absence of alpha-helix 2 in the appendant structure region the major contributor to structural instability of human cystatin C?

Zhou

Qin

et al. 2019

Journal of Biomolecular Structure and Dynamics

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“…In addition, analysis on docking dimer has shown that the distorted AS was in favor of intermolecular interactions between two cystatin monomers. Data from an independent theoretical derived algorithm as well as biological experiments also support this hypothesis (Yu et al, 2012).…”

Section: Structural and Dynamic Properties Of Amyloid Mutant CC I66q mentioning

confidence: 71%

“…The MD results showed that both the I66Q and I108T mutants exhibited relatively large secondary structure changes and obvious expanding tendency of hydrophobic core compared to wild-type cC (Yu et al, 2010(Yu et al, , 2012. More importantly, the appendant structure (AS) of the typical amyloid mutant cC I66Q showed a large displacement and distortion toward its hydrophobic core (Yu et al, 2012).…”

Section: Structural and Dynamic Properties Of Amyloid Mutant CC I66q mentioning

confidence: 97%

Roles of hydrophobic and hydrophilic forces on maintaining amyloid-prone cystatin structural stability

Song¹,

Xu²,

Shen³

et al. 2013

Journal of Biomolecular Structure and Dynamics

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Steered molecular dynamics simulation of the binding of the β2 and β3 regions in domain-swapped human cystatin C dimer

Zhang

et al. 2012

J Mol Model

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The crystal structure of the human cystatin C (hCC) dimer revealed that a stable twofold-symmetric dimer was formed via 3D domain swapping. Domain swapping with the need for near-complete unfolding has been proposed as a possible route for amyloid fibril initiation. Thus, the interesting interactions that occur between the two molecules may be important for the further aggregation of the protein. In this work, we performed steered molecular dynamics (SMD) simulations to investigate the dissociation of the β2 and β3 strands in the hCC dimer. The energy changes observed during the SMD simulations showed that electrostatic interactions were the dominant interactions involved in stabilizing the two parts of the dimer during the early stages of SMD simulation, whereas van der Waals (VDW) interactions and electrostatic interactions were equally matched during the latter stages. Furthermore, our data indicated that the two parts of the dimer are stabilized by intermolecular hydrogen bonds among the residues Arg51 (β2), Gln48 (β2), Asp65 (β3), and Glu67 (β3), salt bridges among the residues Arg53 (β2), Arg51 (β2), and Asp65 (β3), and VDW interactions among the residues Gln48 (β2), Arg51 (β2), Glu67 (β3), Asp65 (β3), Phe63 (β3), and Asn61 (β3). The residues Gln48 (β2), Arg51 (β2), Asp65 (β3) and Glu67 (β3) appear to be crucial, as they play important roles in both electrostatic and VDW interactions. Thus, the present study determined the key residues involved in the stabilization of the domain-swapped dimer structure, and also provided molecular-level insights into the dissociation process of the hCC dimer.

show abstract

Appendant structure plays an important role in amyloidogenic cystatin dimerization prior to domain swapping

Cited by 6 publications

References 30 publications

Is the absence of alpha-helix 2 in the appendant structure region the major contributor to structural instability of human cystatin C?

Is the absence of alpha-helix 2 in the appendant structure region the major contributor to structural instability of human cystatin C?

Roles of hydrophobic and hydrophilic forces on maintaining amyloid-prone cystatin structural stability

Steered molecular dynamics simulation of the binding of the β2 and β3 regions in domain-swapped human cystatin C dimer

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