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. 2010 Oct;30(5):331-6.
doi: 10.3109/10799893.2010.513842.

The dopamine D(4) receptor, the ultimate disordered protein

Amina S Woods  1
Affiliations

The dopamine D(4) receptor, the ultimate disordered protein

Amina S Woods. J Recept Signal Transduct Res. 2010 Oct.

Abstract

The human D4 dopamine receptor is a synaptic neurotransmitter receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its structure makes it a very unusual and interesting G protein-coupled receptor (GPCR) as it has several polymorphic variants of its gene in the region encoding the third intracellular loop (IL3). This region contains from two to seven or more similar 48 base pair repeats. These repeats cause this protein to have a very high disorder index and this, in turn, makes it very interactive with other proteins. Among GPCRs in general, the unusually proline-rich IL3 is unique to the D4 receptor (D4R). We believe that, as in the D2R, this region of the receptor plays a role in it's interaction with other receptors.

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Conflict of interest statement

Declaration of interest

This research was supported by the Intramural Research Program of the National Institute on Drug Abuse, NIH. The authors thank the Office of National Drug Control Policy (ONDCP) for instrumentation funding, without which this and other projects could not have been accomplished.

Figures

Figure 1
Figure 1
(A) Location of Arg-rich epitope. (B) AKAP anchoring kinases and phosphatases.
Figure 2
Figure 2
Mass spectrum showing the non-covalent complex formed between the phosphorylated and non-phosphorylated the epitopes of the D4R and A2AR.
Figure 3
Figure 3
T model of the D4,4 repeats (A) third intracellular loop (IL3) has more α-helices than the D4,7 repeats-IL3 (B).
Figure 4
Figure 4
Shows graphs of the disorder index of the D2, D3 and D4 (four and seven repeat) third intracellular loop The D4-7 is twice as disordered as the D2 or D3, therefore it is more interactive.
See this image and copyright information in PMC

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