Is the process of high-throughtput determination
of 3-D structures of Biological macromolecules
Provision of enough structural templates to
facilitate homology modeling of most
proteins.
Structural elucidation of complete biological
pathway
To determine new protein folds
to develop improved methods that will result in
high-throughput biology and protein structure
determination
To determine the functions of unknown
proteins
The structure will reveal the fold of the protein
The structure will
reveal the active site
The structure may reveal
evolutionary links
between proteins lacking
sequence similarity
The structure may reveal the function of the protein
Complete organisms;
thermophilic, mesophilic or halophilic
eukaryotic or prokaryotic
HUMAN DISEASE
Targets in this area of structural genomics are G-protein coupled receptors,
ion channels and kinases etc.
The development of techniques to allow over-expression, purification and
crystallization of these targets is required and in progress
Develop technologies necessary for large-scale initiatives
develop high-throughput (HTP) cloning
develop high-throughput expression
develop high-throughput purification
STRUCTURE DETERMINATION
Protein
<20 kDa
Protein (>20kDa)
Insoluble
Soluble
N15 C13 Label
Protein-Protein
Interactions
NMR
Aggregated, Unfolded
Folded
Co-Expression
Expression
Purification
Crystal Trials
Limited
Proteolysis
Stable Domain
Protein-Protein
Interactions
Co-Expression
Structure
The first phase of the Protein Structure Initiative (PSI-1) lasted from June 2000 until
September 2005, and had a budget of $270 million funded primarily by NIGMS
The second phase of the Protein Structure Initiative (PSI-2) lasted from July 2005 to June 2010
PSI-2 had a five-year budget of $325 million provided by NIGMS
BIGS - Bacterial Targets at IGS-CNRS, France
BSGC - Berkeley Structural Genomics Center, USA
CESG - Center for Eukaryotic Structural Genomics, USA
ISPC - Israel Structural Proteomics Center, Isreal
JCSG - Joint Center for Structural Genomics, USA
MCSG - The Midwest Center for Structural Genomics, USA, UK, Canada
NESG - Northeast Structural Genomics Consortium, USA
NYSGRC - New York SGXRC - New York Structural Genomics Research Consortium, USA
OPPF - Oxford Protein Production Facility, UK
PSF - Protein Structure Factory, Germany
RIKEN - RIKEN Structural Genomics Initiative, Japan
S2F - Structure 2 Function Project
SECSG - SouthEast Collaboratory for Structural Genomics, USA
SGPP - Structural Genomics of Pathogenic Protozoa Consortium, USA
SPEX Db - (BSGI) - Montreal-Kingston Bacterial Structural Genomics Initiative, Canada
SPINE - Structural Proteomics in Europe, EU
TB - Mycobacterium tuberculosis (TB) Structural Genomics Consortium, 70 labs from 12 countries
XMTB - Mycobacterium Tuberculosis Structural Proteomics Project, Germany
PSI grant period
PSI-2 grant year 2005
PSI-2 grant year 2006
PSI-2 grant year 2007
PSI-2 grant year 2008
PSI-2 grant year 2009
PSI-2 grant extension
PSI-2 total depositions
PSI-3 grant year 2010
PSI-3 total depositions
PSI-1 + PSI-2 + PSI-3
LSC
390
620
682
796
822
217
3527
280
377
4804
ALL-PSI
427
700
718
818
879
244
3786
283
381
5583
Production stage
cloned
Expression tested
Expressed (E > 0)
Expressed-Soluble (S > 0)
Expressed-Soluble (ES >= 9)
Fermented
Purified (>= 0.5 mg yield)
HSQC spectra recorded
"Good" HSQC spectra
HTP crystal screening
Crystal hit
X-Ray structures
NMR structures
Total structures
NESG targets
23,695
22,159
16,888
12,453
9,946
7,271
4,848
2,597
1,353
2,522
1,295
547
452
958
Human proteins
Production stage
NESGtargets
cloned
Expression tested
Expressed (E > 0)
Expressed-Soluble (S > 0)
Expressed-Soluble (ES >= 9)
Fermented
Purified (>= 0.5 mg yield)
HSQC spectra recorded
"Good" HSQC spectra
HTP crystal screening
Crystal hit
X-Ray structures
NMR structures
Total structures
5,479
5,046
3,986
2,599
2,051
1,097
813
422
235
320
130
35
66
93