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Examples from the PYL/PYR Family
IntroductionIntroduction
The 3D structure of abscisic acid (ABA), a plant growth hormone, () is shown in the applet without hydrogens. Abscisic acid binds to a family of proteins - pyrabactin resistance (PYR), PYR-like (PYL) or regulatory components of ABA receptor (RCAR) - which have been found to be involved in ABA signalling,
[1]
[2]
and the structures of some family members have been determined.
[3]
[4]
[5]
The structures of some of these receptors have bound ABA as well as a bound member of a type 2C protein phosphatase (PP2C) family.
Abscisic acid bound to PYR1 dimerAbscisic acid bound to PYR1 dimer
Abscisic acid bound to subunit B of the . Evidence indicates that the dimeric PYR1 is the biological unit even in the absence of ABA.
[3]
Subunit A does not contain ABA, but is in the ABA binding pocket.
Inter-dimer attractive forces: Several of the important interactions are which are part of the large α-helix,, a between Arg (blue N on side chain) in subunit B and Leu (red oxygen carbonyl) in subunit A and a lower on the α-helix, also scene shows all of the above residues in spacefill. All of these residues overlaid with computed surface
[6]
of . The pockets are joined in one continuous surface with the surfaces of the two subunits being fully connected in the area below the inter-dimer attractions. Dimer in spacefill overlaid with .
Conformation differences due to ABA binding: buried in the ABA binding sites formed by the surface pockets.
[6]
Red spheres (water molecules) on the left are in the ABA binding site of subunit A, and red and gray atoms on the right are part of ABA bound to subunit B. Simplify view by showing only the pockets
[7]
of the two . Rotate the structure to observe that the site binding water is open to the surface, but the ABA binding site is not. Surface
[7]
superimposed on the of the protein more clearly shows that the bound ABA is completely covered by the protein, but the water can be seen in the other subunit since the residues have not moved in subunit A as in B.
One aspect of the change in conformation is the movement of the "Pro-Cap" sequence
[3]
in B subunit (green) but not in A subunit; this sequence in both subunits are seen here in spacefill. Pro-Cap sequence of subunit B has moved over top of the ABA site, but the binding site (presented as a surface
[8]
) in A is completely exposed. With ABA binding the pivotes between Ile84 and Asn90 of the B subunit and covers the ABA. An important component of this movement is the of Pro88. This change in Pro moves the positions of the Leu87 and Ala89 side chains which along with the Pro are seen in ball & stick. Compare the positions of these residues of B subunit with the positions of the corresponding residues in A in the next scene which has the structure . Movement of the
[3]
(Glu114 - Thr118) secures the ABA. Notice that Arg116 extends toward the A subunit and hydrogen bonds with the Leu carbonyl in Pro-Cap sequence of A.
Another way of viewing these differences in conformation is to align two structures containing the different conformations. dimeric PYR1 binding ABA
[3]
(red) aligned with dimeric PYL1 not binding ABA
[4]
(blue)
[9]
Observe that the secondary and tertiary structures are much the same, but some parts of the structure are better aligned than others. When the two models are , it appears that PYR1 is more compact than PYL1.
[10]
the above two structures alternating with ABA shown with PYL1, even though it is not bound to it, as well as PYR1.
[11]
Observe that a loop and β-strand comes over the top of ABA in PYR1 in ways that it does not in PYL1. Water in the ABA binding sites of the A subunits is also being displayed. positions of 'Pro-Cap',
[3]
also called 'Gate',
[4]
sequences. As seen in B subunit of PYR1 which binds ABA, this sequence of amino acids moves to cover ABA, but with the PYR1 A subunit and the two subunits of PYL1 which do not bind ABA the sequence does not move. positions of 'Leu-Lock'
isosurface minset 1000 ignore (A8S or HOH) POCKET cavity 1.0 sasurface 0.2
expanded residues: 59, 83, 88, 89, 92, 108, 110, 117, 120, 159, 163, 83-90, 114-118, 147-159
"../images/c/c4/Expand_residues.jvxl"
two smaller pockets: 59, 83, 88, 89, 92, 108, 110, 117, 120, 159, 163
"../images/3/39/Two_binding_pockets.jvxl"
Notes and ReferencesNotes and References
- ↑ Ma Y, et al.. Science. 324, 1064 (2009).
- ↑ Park S.-Y., et al.. Science. 324, 1068 (2009).
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Nishimura N, et al.. "Structural Mechanism of Abscisic Acid Binding and Signaling by Dimeric PYR1". Science. Dec 4 2009, 326, 1373-9.
- ↑ 4.0 4.1 4.2 Melcher,K, et. al.. "A gate-latch-lock mechanism for hormone signalling by abscisic acid receptors". Nature. Dec 3 2009, 462, 602-8; doi:10.1038/nature08613.
- ↑ Miyazono,K, et. al.. "Structural basis of abscisis acid signalling". Nature. Dec 3 2009, 462, 609-14; doi:10.1038/nature08583.
- ↑ 6.0 6.1 Computed by selecting both subunits & using Jmol command 'isosurface minset 1000 ignore (A8S or HOH) POCKET sasurface 0.5' was run.
- ↑ 7.0 7.1 Computed by selecting AC1 site, Pro-Cap, Leu-Lock, Recoil motif (residue #'s: 59, 83, 88, 89, 92, 108, 110, 117, 120, 159, 163, 83-90, 114-118, 147-159) & using Jmol command: isosurface minset 1000 ignore (A8S or HOH) POCKET cavity 1.0 sasurface 0.2
- ↑ The surfaces in both subunits were computed by selecting the AC1 sites of both subunits (residue #'s: 59, 83, 88, 89, 92, 108, 110, 117, 120, 159, 163) & using Jmol command: isosurface minset 1000 ignore (A8S or HOH) POCKET cavity 1.0 sasurface 0.2
- ↑ 3K3K.pdb & 3KAY.pdb were aligned using the Jmol command 'compare {2.1} {1.1} SUBSET {spine} ATOMS {156-180:A or 156-180:B} {182-208:A or 182-208:B}, {6-21:A or 6-21:B} {37-48:A or 37-48:B}, {41-50:A or 41-50:B} {68-77:A or 68-77:B} ROTATE TRANSLATE', and then using the Jmol command 'write' a pdb file containing the coordinates of both structures was generated. In this pdb file model 1.1 is PYL1 (3KAY.pdb) and model 1.2 is PYR1 (3K3K.pdb) Location:/wiki/index.php/Image:3k3k3kay.pdb.
- ↑ This pdb file is a modification of 3k3k3kay.pdb described in the above note. A third model was added by copying from model 1.2 the coordinates of ABA & its associated water. Location:/wiki/index.php/Image:3k3k3kay_3models.pdb
- ↑ This is accomplished in Jmol by setting backgroundModel to 3 before activating animation. The effect is to always display model 3 as it cycles through the three models.