PDBsum entry 2hes

Biosynthetic protein

PDB id: 2hes

Contents

Protein chain

308 a.a. *

Metals

_CA

Waters ×301

* Residue conservation analysis

PDB id:

2hes

Name:

Biosynthetic protein

Title:

Cytosolic iron-sulphur assembly protein- 1

Structure:

Ydr267cp. Chain: x. Engineered: yes

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Gene: ydr267cp. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.70Å R-factor: 0.226 R-free: 0.275

Authors:

V.Srinivasan,H.Michel,R.Lill,J.A.N.Daili,A.J.Pierik

Key ref:

V.Srinivasan et al. (2007). Structure of the yeast WD40 domain protein Cia1, a component acting late in iron-sulfur protein biogenesis. Structure, 15, 1246-1257. PubMed id: 17937914 DOI: 10.1016/j.str.2007.08.009

Date:

22-Jun-06 Release date: 03-Jul-07

Protein chain

Q05583  (CIAO1_YEAST) -  Cytosolic iron-sulfur protein assembly protein 1 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 330 a.a.

Struc: 308 a.a.

DOI no: 10.1016/j.str.2007.08.009

Structure 15:1246-1257 (2007)

PubMed id: 17937914

Structure of the yeast WD40 domain protein Cia1, a component acting late in iron-sulfur protein biogenesis.

V.Srinivasan, D.J.Netz, H.Webert, J.Mascarenhas, A.J.Pierik, H.Michel, R.Lill.

ABSTRACT

The WD40-repeat protein Cia1 is an essential, conserved member of the cytosolic iron-sulfur (Fe/S) protein assembly (CIA) machinery in eukaryotes. Here, we report the crystal structure of Saccharomyces cerevisiae Cia1 to 1.7 A resolution. The structure folds into a beta propeller with seven blades pseudo symmetrically arranged around a central axis. Structure-based sequence alignment of Cia1 proteins shows that the WD40 propeller core elements are highly conserved. Site-directed mutagenesis of amino acid residues in loop regions with high solvent accessibility identified that the conserved top surface residue R127 performs a critical function: the R127 mutant cells grew slowly and were impaired in cytosolic Fe/S protein assembly. Human Ciao1, which reportedly interacts with the Wilms' tumor suppressor, WT1, is structurally similar to yeast Cia1. We show that Ciao1 can functionally replace Cia1 and support cytosolic Fe/S protein biogenesis. Hence, our structural and biochemical studies indicate the conservation of Cia1 function in eukaryotes.

Selected figure(s)

Figure 3.
Figure 3. Comparison of the 3D Structures of Cia1 and Gβ
Superposition of the Cα coordinates of Gβ (PDB code: 1TBG) and the crystal structure coordinates of yeast Cia1. The superposition was computed by using the least-squares algorithm in the program O (Jones et al., 1991).

Figure 4.
Figure 4. Amino Acid Sequence Conservation at the Surface of Cia1
(A) Location of the residues exchanged by site-directed mutagenesis (see Figure 2) from a top view looking down the central propeller axis and a bottom view obtained by rotation of 180°.
(B) Representation of the conservation of amino acid residues in Cia1 from top and bottom views. The degree of conservation is indicated by the intensity of the red color. The position of the crucial residue R127 is highlighted in purple. Amino acid sequences (67 in total) of Cia1 homologs were collected from various databases by blastp and tblastn searches. After CLUSTAL W alignment (Thompson et al., 1994), the degree of conservation was calculated by using the program ConSurf (Landau et al., 2005). Red, orange, and light-orange colors correspond to residues with a conservation score above the 9^th, between the 9^th and 8^th, and between the 8^th and 7^th decile, respectively.
(C) Same as in (B), but for the side views. The yellow markers in (B) and (C) indicate the respective sides of the Cia1 structure. The figure was prepared by using PyMol (http://www.pymol.org) (DeLano, 2002).

The above figures are reprinted by permission from Cell Press: Structure (2007, 15, 1246-1257) copyright 2007.

Figures were selected by the author.