PDBsum entry 1wa9

Circadian rhythm

PDB id: 1wa9

Contents

Protein chains

318 a.a. *

Waters ×6

* Residue conservation analysis

PDB id:

1wa9

Name:

Circadian rhythm

Title:

Crystal structure of the pas repeat region of the drosophila clock protein period

Structure:

Period circadian protein. Chain: a, b. Fragment: pas repeat region, residues 232-599. Synonym: clock-6 protein, clk-6. Engineered: yes

Source:

Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PDB file)

Resolution:

3.15Å R-factor: 0.228 R-free: 0.277

Authors:

O.Yildiz,M.Doi,I.Yujnovsky,L.Cardone,A.Berndt,S.Hennig,S.Schulze, C.Urbanke,P.Sassone-Corsi,E.Wolf

Key ref:

O.Yildiz et al. (2005). Crystal structure and interactions of the PAS repeat region of the Drosophila clock protein PERIOD. Mol Cell, 17, 69-82. PubMed id: 15629718 DOI: 10.1016/j.molcel.2004.11.022

Date:

25-Oct-04 Release date: 12-Jan-05

Protein chains

P07663  (PER_DROME) -  Period circadian protein from Drosophila melanogaster

Seq: 1224 a.a.

Struc: 318 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/j.molcel.2004.11.022

Mol Cell 17:69-82 (2005)

PubMed id: 15629718

Crystal structure and interactions of the PAS repeat region of the Drosophila clock protein PERIOD.

O.Yildiz, M.Doi, I.Yujnovsky, L.Cardone, A.Berndt, S.Hennig, S.Schulze, C.Urbanke, P.Sassone-Corsi, E.Wolf.

ABSTRACT

PERIOD proteins are central components of the Drosophila and mammalian circadian clock. Their function is controlled by daily changes in synthesis, cellular localization, phosphorylation, degradation, as well as specific interactions with other clock components. Here we present the crystal structure of a Drosophila PERIOD (dPER) fragment comprising two tandemly organized PAS (PER-ARNT-SIM) domains (PAS-A and PAS-B) and two additional C-terminal alpha helices (alphaE and alphaF). Our analysis reveals a noncrystallographic dPER dimer mediated by intermolecular interactions of PAS-A with PAS-B and helix alphaF. We show that alphaF is essential for dPER homodimerization and that the PAS-A-alphaF interaction plays a crucial role in dPER clock function, as it is affected by the 29 hr long-period perL mutation.

Selected figure(s)

Figure 2.
Figure 2. Domain Architecture and 3D Structure of Drosophila PERIOD(A) Domain architecture of full-length Drosophila PERIOD. The two PAS (PER-ARNT-SIM) domains (PAS-A and PAS-B), the cytoplasmic localization domain (CLD), nuclear localization signals (NLS), the conserved C-domain, the threonine-glycine (TG) repeat region, and the dCLK:CYC inhibition domain (CCID) are shown schematically. The interacting clock proteins TIMELESS (TIM), DOUBLETIME (DBT), and CRYPTOCHROME (dCRY) are depicted at their respective binding sites. per^L,S/T, long- and short-period mutation sites; S/M, short-mutable region. The crystallized fragment is represented as black bar.(B) Ribbon presentation of the dPER dimer. Molecule 1 is shown in red and gray, molecule 2 in yellow and blue. The loop insertions of dPER PAS-A (αC-βC, βC-βD, and βD-βE) are labeled, and disordered regions are depicted as dotted lines.(C) Superposition of dPER molecules 1 (red) and 2 (blue). Molecule 2 is superimposed onto PAS-B of molecule 1. The left orientation shows the PAS-A and -B domain faces covered by α helices, and the right (roughly 180° rotated) orientation shows the uncovered β sheet surfaces.

Figure 5.
Figure 5. Comparison of dPER PAS Domains with Sensory PAS/LOV Domain Structures(A) Superposition of dPER PAS-A and PAS-B with sensory PAS/LOV domains (stereoview). The PAS domains of dPER molecule 1 (PAS-A, gray and thick line; PAS-B, red and thick line) are superimposed on the PAS domains of the human ether-a-go-go-related gene potassium channel (HERG, gray and thin line; 1BYW) (Morais Cabral et al., 1998), human PAS kinase (hPASK PAS-A, dark blue; 1LL8) (Amezcua et al., 2002), bacterial FixL histidine kinase (FixL, green; 1DP6) (Gong et al., 1998), Adantium Phototropin PHY3 (PHY3 LOV2: yellow, 1G28) (Crosson and Moffat, 2001), bacterial Photoactive Yellow Protein (PYP: cyan, 2PYP) (Borgstahl et al., 1995) and human HIF-2α (HIF-2α PAS-B: magenta, 1P97) (Erbel et al., 2003) (PDB). The loop insertions of dPER PAS-A (αC-βC, βC-βD, and βD-βE) are labeled.(B) Superposition of dPER PAS-A (gray) and PAS-B (red) of molecule 1 and the chromophores FMN of PHY3 LOV2 (yellow), heme of FixL (green) and 4-hydroxycinnamic acid of PYP (CIN, cyan). The βD′-βE′ loop of molecule 2 including Trp482 is shown in dark blue.(C) Structure-based sequence alignment of dPER-PAS-A and dPER-PAS-B with HIF-2α PAS-B, FixL, PHY3 LOV2, C.reinhardtii phot1 LOV1 (CR LOV1, PDB 1N9L/N/O) (Fedorov et al., 2003), PYP, hPASK PAS-A and HERG (PDB IDs as in 5A).

The above figures are reprinted by permission from Cell Press: Mol Cell (2005, 17, 69-82) copyright 2005.

Figures were selected by an automated process.