PDBsum entry: 1rlu

Cell cycle, signaling protein

PDB id: 1rlu

Contents

Protein chains

305 a.a. *

Ligands

GSP

GOL

Waters ×270

* Residue conservation analysis

PDB id:

1rlu

Name:

Cell cycle, signaling protein

Title:

Mycobacterium tuberculosis ftsz in complex with gtp-gamma-s

Structure:

Cell division protein ftsz. Chain: a, b. Engineered: yes

Source:

Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: ftsz, rv2150c, mt2209, mtcy270.18, mb2174c. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.08Å R-factor: 0.182 R-free: 0.224

Authors:

A.K.W.Leung,E.L.White,L.J.Ross,R.C.Reynolds,J.A.Devito,D.W.B

Key ref:

A.K.Leung et al. (2004). Structure of Mycobacterium tuberculosis FtsZ reveals unexpected, G protein-like conformational switches. J Mol Biol, 342, 953-970. PubMed id: 15342249 DOI: 10.1016/j.jmb.2004.07.061

Date:

26-Nov-03 Release date: 31-Aug-04

Protein chains

P64170  (FTSZ_MYCTU) -  Cell division protein FtsZ

Seq: 379 a.a.

Struc: 305 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: protein complex (3 terms)
• Biological process: growth (6 terms)
• Biochemical function: nucleotide binding (5 terms)

DOI no: 10.1016/j.jmb.2004.07.061

J Mol Biol 342:953-970 (2004)

PubMed id: 15342249

Structure of Mycobacterium tuberculosis FtsZ reveals unexpected, G protein-like conformational switches.

A.K.Leung, E.Lucile White, L.J.Ross, R.C.Reynolds, J.A.DeVito, D.W.Borhani.

ABSTRACT

We report three crystal structures of the Mycobacterium tuberculosis cell division protein FtsZ, as the citrate, GDP, and GTPgammaS complexes, determined at 1.89, 2.60, and 2.08A resolution. MtbFtsZ crystallized as a tight, laterally oriented dimer distinct from the longitudinal polymer observed for alphabeta-tubulin. Mutational data on Escherichia coli FtsZ suggest that this dimer interface is important for proper protofilament and "Z-ring" assembly and function. An alpha-to-beta secondary structure conformational switch at the dimer interface is spatially analogous to, and has many of the hallmarks of, the Switch I conformational changes exhibited by G-proteins upon activation. The presence of a gamma-phosphate in the FtsZ active site modulates the conformation of the "tubulin" loop T3 (spatially analogous to the G-protein Switch II); T3 switching upon gamma-phosphate ligation is directly coupled to the alpha-to-beta switch by steric overlap. The dual conformational switches observed here for the first time in an FtsZ link GTP binding and hydrolysis to FtsZ (and tubulin) lateral assembly and Z-ring contraction, and they are suggestive of an underappreciated functional analogy between FtsZ, tubulin and G-proteins.

Selected figure(s)

Figure 1.
Figure 1. MtbFtsZ forms an unexpected secondary structure conformational switch at its unique dimer interface. A, The GTPgS complex (subunit A, yellow; subunit B, brown) is viewed from the "inside" of a corresponding microtubule. GTPgS bound to the subunit A active site is shown as a space-filling model (nitrogen, blue; oxygen, red; phosphorous, yellow-green; carbon, grey; sulfur, purple). A ghost-like GTPgS is shown in subunit B for reference. The switch elements sH2 (subunit A) and sb2 (subunit B) at the subunit interface within the dimer are highlighted in light blue. The active site loops T1, T3, T4, and T7 are lavender. The two MtbFtsZ subunits are related by a vert, similar 92° rotation about the vertical axis (grey); this axis is canted by vert, similar 50° from the ab-tubulin protofilament axis (light green), drawn with the arrowhead pointing in the (+)-direction. B, Rotated by 90° about a horizontal axis (from the top in A), to better illustrate the dimer interface. C, Comparison of the MtbFtsZ dimer with the ab-tubulin protofilament (PDB entry 1jff).10 Subunit A was aligned with the exchangeable (E) a-tubulin subunit (blue), which contains GDP (green) in its active site and a bound Taxol (purple) molecule. The two adjacent non-exchangeable (N) b-tubulin subunits (black) in the protofilament contain GTP (red). The protofilament axis is vertical.

Figure 4.
Figure 4. The conformational switch. The region between b2 and b3 adopts two distinct conformations in MtbFtsZ. The active sites of subunits A (A) and B (B) are shown, colored as in Figure 1. The ordered T3 loop ("Switch II") in subunit A is apposed to the g-thiophosphate of GTPgS and to the sH2 switch a-helix ("Switch I"). In subunit B, T3 is disordered (balls), and the switch has "switched" to the sb2 b-strand conformation. Also shown in B is the a-helix H5 of subunit A (yellow) which blocks the subunit B active site, the collapse inward of T4, the unraveling of H8, and the bend of H10 away from the active site. C, The switch in the b-conformation collides with T3. In this stereoview, subunit A is shown as a yellow, light blue (sH2), and lavender (T3 and T4) ribbon. The b2-sb2-b3 portion of subunit B, aligned on A, is drawn as a brown tube. Note how the extension of sb2 collides (red arrow) with T3 when the latter is closed around GTPgS (as in subunit A). D, Details of the hydrogen bond network that reinforces the switch. The positions and hydrogen bonds formed by the switch residues Asn41, Thr42, and Asp43 and by T4 residue Thr106 are distinct. The side chain of Asp43, as found in sb2, is spatially incompatible with binding the g-phosphate of GTP.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 342, 953-970) copyright 2004.

Figures were selected by the author.