PAS domain

A Per-Arnt-Sim (PAS) domain is a protein domain found in all kingdoms of life.^[2] Generally, the PAS domain acts as a molecular sensor, whereby small molecules and other proteins associate via binding of the PAS domain.^[3][4][5] Due to this sensing capability, the PAS domain has been shown as the key structural motif involved in protein-protein interactions of the circadian clock, and it is also a common motif found in signaling proteins, where it functions as a signaling sensor.^[6][7]

Discovery

PAS domains are found in a large number of organisms from bacteria to mammals. The PAS domain was named after the three proteins in which it was first discovered:^[8]

• Per – period circadian protein
• Arnt – aryl hydrocarbon receptor nuclear translocator protein
• Sim – single-minded protein

Since the initial discovery of the PAS domain, a large quantity of PAS domain binding sites have been discovered in bacteria and eukaryotes. A subset called PAS LOV proteins are responsive to oxygen, light and voltage.^[9]

Structure

Although the PAS domain exhibits a degree of sequence variability, the three-dimensional structure of the PAS domain core is broadly conserved.^[10] This core consists of a five-stranded antiparallel β-sheet and several α-helices. Structural changes, as a result of signaling, predominantly originate within the β-sheet. These signals propagate via the α-helices of the core to the covalently-attached effector domain.^[11] In 1998, the PAS domain core architecture was first characterized in the structure of photoactive yellow protein (PYP) from Halorhodospira halophila.^[10] In many proteins, a dimer of PAS domains is required, whereby one binds a ligand and the other mediates interactions with other proteins.^[5]

Examples of PAS in organisms

The PAS domains that are known share less than 20% average pairwise sequence identity, meaning they are surprisingly dissimilar.^[10] PAS domains are frequently found on proteins with other environmental sensing mechanisms. Also, many PAS domains are attached to photoreceptive cells.^[12]

Bacteria

Often in the bacterial kingdom, PAS domains are positioned at the amino terminus of signaling proteins such as sensor

In the presence of light, White Collar-1 (WC-1) and White Collar-2 (WC-2) dimerizes via mediation by the PAS domains, which activates translation of FRQ.^[13]

Drosophila

In the presence of light, CLK and CYC attach via a PAS domain, activating the translation of PER, which then associates to Tim via the PER PAS domain. The following genes contain PAS binding domains: PER, Tim, CLK, CYC.

Arabidopsis

A PAS domain is found in the ZTL and NPH1 genes. These domains are very similar to the PAS domain found in the Neurospora circadian-associated protein WC-1.^[14]

Mammals

The circadian clock that is currently understood for mammals begins when light activates