Structure prediction and evolution of CHASE domain

Jakub Pas1,2, Jan Barciszewski1 1. Institute of Bioorganic Chemistry Polish Academy of Science,

Poznan, Poland 2. Bioinfobank Institute, Poznan, Poland

Characteristics of CRE1 cytokinin receptor

1000 aa long N terminal ligand binding domain ( 300 aa) Histidine kinase domain at the C terminus

followed by two receiver domains T 278 mutation causes the loss of function A part of the two component system

CHASE

200 – 230 aa Present in bacteria, lower eukaryotes and

plants Bound at the C terminus Binds cytokinins and peptides Helices at the both ends Two internal helices divided by strands (a + b

fold) Mechanism of ligand binding and evolutional

relationships are unknown.

Modelling ProcesMetaserver

3D Jury

Modeller Verrify 3D

Domain Split

Domain selection

Structure Prediction

(Profile)

Structure Evaluation

Molecular modelling Quality check

Alignment corection

Query sequence (CRE1)

Final Model

Profile - profile fold recognition method

1st pass: Query sequence vs Sequence Database

2nd pass: Query Profile vs Profile Database

alignment

alignment

Evolutionary relationships to CHASE domain

(GRDB-Gene Related Data Base)

1jogA - sensory domain of the membraneous two-component fumarate - sensor Dcus from E. coli, 1p0zA - sensor kinase cita. 1e4eA, 1ehiA - D-Alanine-D-lactate ligase.

Structures of receptor domains selected by 3DHit as related to 1joga.

Domain 3d-hit score

PDB code

Function Organism Ligand

CACHE 84.3 1p0z Ca2+ channels and chemotaxis receptors

K.pneumoniae Citrate Anion

GAF 55.6 1mc0 cGMP phosphodiesterase, adenyl cyclase, FhlA domain

M.musculus Cyclic guanosine monophosphate

PAS/PYP 47.2 1f98 Periodic clock protein, aryl hydrocarbon receptor and single-minded protein/Photoactive Yellow Protein

E. halophila 4'-Hydroxycinnamic Acid

Profiln 46.2 1g5u monomeric actin binding H. brasiliensis Actin ACT - 1psdA1 Aspartate kinase –

chorismate mutase – TyrA E.coli Nicotinamide-

Adenine-Dinucleotide

Topological representation and evolution of PYP family

Molecular model of CRE1a receptor from A. thaliana with trans-zeatin.

Conclusions

CRE1 and 1mc0 are located on the same clade and may have common origin

Cre1 is lacking a strand they are structurally much more similar to each other then to other members of PAS/PYP superfamily

The ligands bound by both domains are also structurally similar

CACHE, PAS/PYP and Profilin form a separate branch. These two groups separated very early in evolution.

Most of the protein-ligand interaction fulfiled by closely related receptors which are diverse in primary structure but share a common structure.