FIGURE 8.

Bound PI(4,5)P₂ can partially occlude the nearby CAP binding site. A, snapshot from an MD simulation in which PI(4,5)P₂ is bound to the binding site determined in the present work. Here, in the absence of CAP, an aliphatic chain of PI(4,5)P₂ occupies the hypothesized CAP binding site. Atoms of PI(4,5)P₂ are shown as spheres, while residues of TRPV1 that may be in contact with both bound PI(4,5)P₂ and bound CAP are shown by a stick model and highlighted by a yellow surface. B, percentage of time in which atoms of PI(4,5)P₂ make contact with specific residues of the CAP binding site in the absence of CAP. Occupancy of the CAP binding site by the aliphatic chain of PI(4,5)P₂ is only partial, and it frequently exits and reenters this site. This suggests that bound PI(4,5)P₂ may partially, but not completely, block the access of CAP to its binding site. C, snapshot from an MD simulation where both CAP and PI(4,5)P₂ occupy their respective binding sites. Atoms of CAP are shown as spheres, while PI(4,5)P₂ is represented by thin lines. D, percentage of time in which atoms of CAP make contact with specific residues of its binding site while PI(4,5)P₂ is bound nearby. CAP stably occupies the hypothesized binding site. E, another snapshot from the same simulation represented in panel C, highlighting contact between PI(4,5)P₂ and CAP. Atoms of PI(4,5)P₂ are shown as spheres, while CAP is represented by thin orange tubes. F, percentage of time in which atoms of PI(4,5)P₂ make contact with specific residues of the CAP binding site while occupied by CAP. The presence of CAP substantially reduces the occupation of the site by the PI(4,5)P₂ aliphatic chain, which can be clearly seen by comparing to panel B.