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PDBsum entry 1rlu

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protein ligands Protein-protein interface(s) links
Cell cycle, signaling protein PDB id
1rlu
Jmol
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    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam  
P9WN95  (FTSZ_MYCTU) -  Cell division protein FtsZ
Seq:
Struc:
379 a.a.
305 a.a.
Key:    Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     protein complex   4 terms 
  Biological process     growth   7 terms 
  Biochemical function     nucleotide binding     3 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.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21413908 D.Awasthi, K.Kumar, and I.Ojima (2011).
Therapeutic potential of FtsZ inhibition: a patent perspective.
  Expert Opin Ther Pat, 21, 657-679.  
20043048 P.Gupta, H.Rajeswari, M.Arumugam, S.Mishra, R.Bhagavat, P.Anand, N.Chandra, R.Srinivasan, S.Indi, and P.Ajitkumar (2010).
Mycobacterium tuberculosis FtsZ requires at least one arginine residue at the C-terminal end for polymerization in vitro.
  Acta Biochim Biophys Sin (Shanghai), 42, 58-69.  
19161972 E.Wilcox, C.McGrath, A.V.Blokhin, R.Gussio, and E.Hamel (2009).
Evidence for a distinct ligand binding site on tubulin discovered through inhibition by GDP of paclitaxel-induced tubulin assembly in the absence of exogenous GTP.
  Arch Biochem Biophys, 484, 55-62.  
18322037 E.C.Hett, and E.J.Rubin (2008).
Bacterial growth and cell division: a mycobacterial perspective.
  Microbiol Mol Biol Rev, 72, 126.  
18436955 R.Jaiswal, and D.Panda (2008).
Cysteine 155 plays an important role in the assembly of Mycobacterium tuberculosis FtsZ.
  Protein Sci, 17, 846-854.  
17043359 K.M.Chung, H.H.Hsu, H.Y.Yeh, and B.Y.Chang (2007).
Mechanism of regulation of prokaryotic tubulin-like GTPase FtsZ by membrane protein EzrA.
  J Biol Chem, 282, 14891-14897.  
17656575 R.Díaz-Espinoza, A.P.Garcés, J.J.Arbildua, F.Montecinos, J.E.Brunet, R.Lagos, and O.Monasterio (2007).
Domain folding and flexibility of Escherichia coli FtsZ determined by tryptophan site-directed mutagenesis.
  Protein Sci, 16, 1543-1556.  
17644520 Y.Chen, D.E.Anderson, M.Rajagopalan, and H.P.Erickson (2007).
Assembly dynamics of Mycobacterium tuberculosis FtsZ.
  J Biol Chem, 282, 27736-27743.  
17068335 M.Thakur, and P.K.Chakraborti (2006).
GTPase activity of mycobacterial FtsZ is impaired due to its transphosphorylation by the eukaryotic-type Ser/Thr kinase, PknA.
  J Biol Chem, 281, 40107-40113.  
15844012 K.Ozawa, T.Harashina, R.Yatsunami, and S.Nakamura (2005).
Gene cloning, expression and partial characterization of cell division protein FtsZ1 from extremely halophilic archaeon Haloarcula japonica strain TR-1.
  Extremophiles, 9, 281-288.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.