8 research outputs found
The movement at the sub-domain level.
<p><b>(A)</b> The C-α displacement of the tip residue H513 on the β hairpin. <b>(B)</b> The C-α displacement of the tip residue D455 on the central channel of the C-terminal. <b>(C)</b> The average folding angle of D2/D3, represented by the angle between C-α of LYS331, ASN366 and HIS513. <b>(D)</b> The average channel radius on the top (black), middle (red) and bottom section (blue). <b>(E)</b> The angle that can be changed between two domains (domain folding angle) is indicated (red arrow), C-α positions of the top K331, middle H513 and bottom D455 are shown in the helicase. The H513 and D455 displacements are shown in grey arrows.</p
The timeline of the major hydrogen bonds formed in the binding pocket during the ATP binding procedure.
<p>The hydrogen bonds formed between the ATP and the <i>cis</i>-residues are plotted in black lines, between ATP and <i>trans</i>-residues are plotted in grey lines, between the binding lock residues are plotted in red lines, and between apical water and the coordinated residues are plotted in blue lines.</p
Domain-scale conformational change.
<p><b>(A)</b> A side view of a monomer in the context of a LTag hexamer, viewing from the outside. The yellow, blue and cyan helices are the alpha-helices H15, H6 and H8 respectively. <b>(B)</b> Bottom view of the monomer. The dotted line with two round ends is the axis, along which, the D2/3 part moves around. The circle with a cross inside indicates the position of the central channel. The red and blue residues are <i>cis</i> and <i>trans</i> residues respectively. <b>(C)</b> A side view of the monomer in the context of the LTag hexamer, viewing from inside of the hexamer. The movement of the tip residue of the β hairpin (H513) is illustrated in a series of red dots. The moving trajectory is about 15° to the axis of the central channel. <b>(D)</b> Side view of the monomer perpendicular to the rotation axis. The D2/D3 movement is illustrated by a series of tip residues, such as H513 and D455. The green, cyan, yellow residues correspond to the position of WS,TS and ATP bound state. The circles in yellow, dark blue and cyan represent the axis position of H15, H6 and H8, respectively. <b>(E)</b> The cooperative iris movement of the D2/D3 domain from the bottom view. <b>(F)</b> The cooperative upwards movement of the β-hairpin along the central channel in a screw manner. The upward arrows represent the H513 movement on the tips of the β-hairpin. The curved arrows illustrate the domain folding movement of D2/D3 along the axes in solid line.</p
The interaction energy profile between the ATP-Mg<sup>2+</sup> complex and the binding pocket.
<p>The negative time slot represents the conformation before the docking stage. The top profile <b>(A)</b> is generated with ε=20, and the bottom profile <b>(B)</b> is generated with ε=40.</p
Lowered pH Leads to Fusion Peptide Release and a Highly Dynamic Intermediate of Influenza Hemagglutinin
Hemagglutinin
(HA), the membrane-bound fusion protein of the influenza
virus, enables the entry of virus into host cells via a structural
rearrangement. There is strong evidence that the primary trigger for
this rearrangement is the low pH environment of a late endosome. To
understand the structural basis and the dynamic consequences of the
pH trigger, we employed explicit-solvent molecular dynamics simulations
to investigate the initial stages of the HA transition. Our results
indicate that lowered pH destabilizes HA and speeds up the dissociation
of the fusion peptides (FPs). A buried salt bridge between the N-terminus
and Asp112<sub>2</sub> of HA stem domain locks the FPs and may act
as one of the pH sensors. In line with recent observations from simplified
protein models, we find that, after the dissociation of FPs, a structural
order–disorder transition in a loop connecting the central
coiled-coil to the C-terminal domains produces a highly mobile HA.
This motion suggests the existence of a long-lived asymmetric or “symmetry-broken”
intermediate during the HA conformational change. This intermediate
conformation is consistent with models of hemifusion, and its early
formation during the conformational change has implications for the
aggregation seen in HA activity