PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons
E-Collection

Related Articles
Community-Nominated Targets
July 2015
Drug Discovery: Solving the Structure of an Anti-hypertension Drug Target
July 2015
Retrospective: 7,000 Structures Closer to Understanding Biology
July 2015
Design and Evolution: Unveiling Translocator Proteins
June 2015
Signaling with DivL
May 2015
Signaling: A Platform for Opposing Functions
May 2015
Signaling: Securing Lipid-Protein Partnership
May 2015
Dynamic DnaK
March 2015
Iron-Sulfur Cluster Biosynthesis
December 2014
Mitochondrion: Flipping for UCP2
December 2014
Mitochondrion: Setting a New TRAP1
December 2014
Power in Numbers
August 2014
Quorum Sensing: A Groovy New Component
August 2014
Quorum Sensing: E. coli Gets Involved
August 2014
iTRAQing the Ubiquitinome
July 2014
Microbiome: The Dynamics of Infection
September 2013
Protein-Nucleic Acid Interaction: A Modified SAM to Modify tRNA
July 2013
Protein-Nucleic Acid Interaction: Versatile Glutamate
July 2013
PDZ Domains
April 2013
Alpha-Catenin Connections
March 2013
Cell-Cell Interaction: A FERM Connection
March 2013
Cell-Cell Interaction: Magic Structure from Microcrystals
March 2013
Cell-Cell Interaction: Modulating Self Recognition Affinity
March 2013
Bacterial Hemophores
January 2013
Archaeal Lipids
December 2012
Membrane Proteome: Capturing Multiple Conformations
December 2012
Lethal Tendencies
October 2012
Symmetry from Asymmetry
October 2012
A signal sensing switch
September 2012
Regulatory insights
September 2012
AlkB Homologs
August 2012
Budding ensemble
August 2012
Targeting Enzyme Function with Structural Genomics
July 2012
The machines behind the spindle assembly checkpoint
June 2012
Chaperone interactions
April 2012
Pilus Assembly Protein TadZ
April 2012
Revealing the Nuclear Pore Complex
March 2012
Topping off the proteasome
March 2012
Twist to open
March 2012
Disordered Proteins
February 2012
Analyzing an allergen
January 2012
Making Lipopolysaccharide
January 2012
Pulling on loose ends
January 2012
Terminal activation
December 2011
The Perils of Protein Secretion
November 2011
Bacterial Armor
October 2011
TLR4 regulation: heads or tails?
October 2011
Ribose production on demand
September 2011
Moving some metal
August 2011
Looking for lipids
July 2011
Ribofuranosyl Binding Protein
June 2011
A molecular switch for neuronal growth
May 2011
Cell wall recycler
May 2011
Added benefits
April 2011
NMR challenges current protein hydration dogma
March 2011
Nitrile Reductase QueF
March 2011
Tip formin
March 2011
Inhibiting factor
February 2011
PASK staying active
February 2011
Tryptophanyl-tRNA Synthetase
February 2011
Regulating nitrogen assimilation
January 2011
Subtle shifts
January 2011
Nitrobindin
December 2010
Function following form
October 2010
tRNA Isopentenyltransferase MiaA
August 2010
Importance of extension for integrin
June 2010
Phytochrome
April 2010
Alg13 Subunit of N-Acetylglucosamine Transferase
February 2010
Hemolysin BL
January 2010
Secretagogin
December 2009
Two-component signaling
December 2009
Network coverage
November 2009
Pseudouridine Synthase TruA
November 2009
Unusual cell division
October 2009
Toxin-antitoxin VapBC-5
September 2009
Salicylic Acid Binding Protein 2
August 2009
Proofreading RNA
July 2009
Ykul structure solves bacterial signaling puzzle
July 2009
Hda and DNA Replication
June 2009
Controlling p53
May 2009
Mitotic checkpoint control
May 2009
Ribonuclease and Ribonuclease Inhibitor
April 2009
The elusive helicase
April 2009
Aquaglyceroporin
March 2009
High-energy storage system
February 2009
A new class of bacterial E3 ubiquitination enzymes
January 2009
Poly(A) RNA recognition
January 2009
Activating BAX
December 2008
Scavenger Decapping Enzyme DcpS
November 2008
Bacteriophage Lambda cII Protein
October 2008
New metal-binding domain
October 2008
Blocking AmtB
September 2008
T-Rex
September 2008
Aspartate Dehydrogenase
August 2008
RNase T
July 2008
Chronophin
May 2008

Research Themes Cell biology

Network coverage

PSI-SGKB [doi:10.1038/fa_psisgkb.2009.48]
Featured Article - November 2009
Short description: A comprehensive atomic-resolution analysis of the centralmetabolic system of Thermotoga maritima sheds light on protein evolution.

The structure of TM1585 of Thermotoga maritima, one of the 478 proteins that make up the central metabolic pathway. Watch this video about the central metabolic pathway of T. maritima. Courtesy of NIGMS

For decades, metabolic pathways have been viewed as a series of chemical reactions, and scientists have worked away at cataloging substrates, reactions and products. Yet it is increasingly clear that this representation no longer adequately describes the mass of genomic and proteomic information we now have about a cell's metabolic system. Viewing this information as a biological network seems to be the way forward.

Now an entire network can be viewed at atomic resolution in three dimensions. All of the 478 proteins forming the central metabolic network of the marine bacterium Thermotoga maritima has been overlayed with structures. This remarkable feat was achieved by PSI JCMM, PSI JCSG, the Department of Bioengineering, University of California at San Diego and the Burnham Institute for Medical Research at La Jolla. Between them, they compiled and analyzed the structures of 120 proteins, solved by the JCSG, other PSI centers, and other structural biology groups, and modeled the remaining 358.

T. maritima is a thermophilic bacterium that thrives at around 80°C. It was first discovered in a geothermal vent and is of interest for two reasons. The first is that from an evolutionary point of view it represents the deepest known branch point in the bacterial domain and it is also one of the slowest-evolving bacterial lineages. The second is that T. maritima metabolizes many carbohydrates, including cellulose and xylan, producing hydrogen as a waste product, and so is a potential source of renewable energy.

The team first constructed a framework for the metabolic network using information gleaned from nearly 150 publications on T. maritima, from which they were able to annotate more than half of the metabolic reactions. They then worked out the remaining interactions using a variety of approaches, including comparison of reactions with those in other similar microorganisms.

The initial framework was tested using flux balance analysis, a mathematical technique that identifies gaps in a network. Eventually, the network consisted of 478 genes, 503 metabolites and 562 intracellular and 83 extracellular reactions. With this information, the team was able to simulate the metabolism of T. maritima at both the biochemical and the molecular level.

Three-dimensional structures of each of the 478 gene products were generated, either by experimental structural biology or through homology modeling. This structural genomic approach added considerable functional information to the network, as it supported the functional assignment of at least 181 proteins.

But to the team's surprise, what caught their eye from the structural information was how few different folds there were in the T. maritima proteins when compared with a random set of proteins. In the 478 proteins in the network, containing a total of 714 domains, there were only 182 different folds; about 300 different folds would be expected for a random protein set. Of the folds, the triosephosphate isomerase (TIM) barrel was most frequent, followed by the Rossmann folds.

The team explored further this non-random fold distribution by looking at just the core-essential group of proteins. This group has a surprisingly large number of folds (111 folds for 177 proteins) compared with the non-essential protein group (92 folds for 203 proteins). This suggests that core-essential proteins carry out unique functions that require specific folds and non-essential tasks can exploit and adapt existing folds.

Maria Hodges

References

  1. Y. Zhang, I. Thiele, D. Weekes, Z. Li, L. Jaroszewski et al. Three-dimensional structural view of the central metabolic network of Thermotoga maritima.
    Science 325, 1544-1549 (2009). doi:10.1126/science.1174671

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health