PDBsum entry: 1xzz

Membrane protein

PDB id: 1xzz

Contents

Protein chain

216 a.a. *

Ligands

GOL

Waters ×130

* Residue conservation analysis

PDB id:

1xzz

Name:

Membrane protein

Title:

Crystal structure of the ligand binding suppressor domain of inositol 1,4,5-trisphosphate receptor

Structure:

Inositol 1,4,5-trisphosphate receptor type 1. Chain: a. Fragment: ip3r suppressor domain (residues 2-223). Synonym: type 1 inositol 1,4,5- trisphosphate receptor, typ receptor, ip3 receptor isoform 1, insp3r1, inositol 1,4,5- trisphosphate-binding protein p400, purkinje cell protein 1 pcd-6. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: itpr1, insp3r, pcd6, pcp1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

1.80Å R-factor: 0.205 R-free: 0.238

Authors:

I.Bosanac,H.Yamazaki,T.Matsu-Ura,T.Michikawa,K.Mikoshiba,M.I

Key ref:

I.Bosanac et al. (2005). Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor. Mol Cell, 17, 193-203. PubMed id: 15664189 DOI: 10.1016/j.molcel.2004.11.047

Date:

13-Nov-04 Release date: 25-Jan-05

Protein chain

P11881  (ITPR1_MOUSE) -  Inositol 1,4,5-trisphosphate receptor type 1

Seq: 2749 a.a.

Struc: 216 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Cellular component: membrane (2 terms)
• Biological process: calcium ion transport (1 term)
• Biochemical function: inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity (1 term)

DOI no: 10.1016/j.molcel.2004.11.047

Mol Cell 17:193-203 (2005)

PubMed id: 15664189

Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor.

I.Bosanac, H.Yamazaki, T.Matsu-Ura, T.Michikawa, K.Mikoshiba, M.Ikura.

ABSTRACT

Binding of inositol 1,4,5-trisphosphate (IP(3)) to the amino-terminal region of IP(3) receptor promotes Ca(2+) release from the endoplasmic reticulum. Within the amino terminus, the first 220 residues directly preceding the IP(3) binding core domain play a key role in IP(3) binding suppression and regulatory protein interaction. Here we present a crystal structure of the suppressor domain of the mouse type 1 IP(3) receptor at 1.8 A. Displaying a shape akin to a hammer, the suppressor region contains a Head subdomain forming the beta-trefoil fold and an Arm subdomain possessing a helix-turn-helix structure. The conserved region on the Head subdomain appeared to interact with the IP(3) binding core domain and is in close proximity to the previously proposed binding sites of Homer, RACK1, calmodulin, and CaBP1. The present study sheds light onto the mechanism underlying the receptor's sensitivity to the ligand and its communication with cellular signaling proteins.

Selected figure(s)

Figure 2.
Figure 2. Structure of Mouse IP[3]R[sup](A) Ribbon diagram of the IP[3]R[sup] Head subdomain (green) and Arm subdomain (yellow).(B) View in (A) rotate by 90°.(C) Section of experimental electron density map contoured at 2.5σ in stereoview.(D) The IP[3]R[sup] (yellow) is superimposed on the β-domain of the IP[3]R[core] (cyan) (PDB accession number 1N4K, residues 236–436). The splice site SI is shown in β-domain of the IP[3]R[core]. The rmsd of the superposition is 2.0 Å. Panels were generated with MOLSCRIPT (Kraulis, 1991), Raster3D (Merrit and Bacon, 1997), and CONSCRIPT software (Lawrence and Bourke, 2000).

Figure 5.
Figure 5. Modeling of β-Trefoil Domains in hRyR1(A) Structure-based sequence alignment between mIP[3]R1 and hRyR1. Location of the 12 β strands in the two β-trefoil domains of hRyR1 is depicted. Residues within the β strands of the two β-trefoil domains in mIP[3]R1 (IP3R-βD1 and IP3R-βD2) and hRyR1 (RyR-βD1 and RyR-βD2) are shown. Residues comprising the linker regions are not shown. Key residues at the interior of the β-trefoil barrel are arranged in three layers referred to as bottom (highlighted in yellow), middle (highlighted in blue), and top (highlighted in green) (Murzin et al., 1992). The bottom layer is comprised of residues just underneath the triangular cap, with the middle and top layers lying parallel to it and away from the cap. The key residues of the triangular cap (highlighted in gray) interact with the residues from the bottom layer of the barrel. Residues of hRyR1 whose mutations lead to MH and CCD are shown in red.(B) Modeled structure of first β-trefoil domain in hRyR1 (RyR-βD1) based on the sequence alignment shown in (A). The model is shown as ribbon diagram in a top panel, with MH and CCD mutations highlighted in red. Surface electrostatic potential, with positive charge depicted in blue and negative charge in red, is plotted in the middle panel. The bottom panel shows surface residue conservation determined from sequence alignment of RyR receptors listed below, with identical residues in magenta and the least conserved residues in green. The highly conserved area (residues R75, Q79, Q93, T99, Y102, R124, D128, K129, L130, F132, T148, H150, P151, A152, S153, K154, Q155, S157, E158, E160, K161, R163, I169, V171, S172, V173, E176, R177, Y178, F194) is observed only on this side of the molecule.(C) View in (B) rotated by 180° with same panel arrangement as in (A).(D) Model of second β-trefoil domain structure of hRyR1 (RyR-βD2) in the same orientation as RyR-βD1 shown in (B).(E) View in (D) rotate by 180°. Panel arrangement is the same as that in (B). For more detail on the modeled structures of RyR-βD1 and RyR-βD2 see Supplemental Figure S1. National Center for Biotechnology Information (NCBI) accession numbers for sequences used in the sequence alignment of RyRs are human RyR1 (J05200), human RyR2 (X98330), human RyR3 (AJ001515), rabbit RyR1 (X15209), rabbit RyR2 (M59743), rabbit RyR3 (X68650), bull frog RyR1 (D21070), bull frog RyR3 (D21071), fruit fly RyR (D17389), and C. elegans RyR (D45899). Homology modeling was performed using Modeller (Sali and Blundell, 1993). Conservation was determined with ConSurf (Armon et al., 2001) and surface representation was generated with GRASP (Nicholls et al., 1991) (middle and bottom panels of [B]–[E]). PyMol (DeLano, 2002) was used in top panels of (B)–(E).

The above figures are reprinted by permission from Cell Press: Mol Cell (2005, 17, 193-203) copyright 2005.

Figures were selected by an automated process.