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macromolecularnanomachines
IN ACTION



       José Ramón Macías
Hi, my name is:



José Ramón Macías
                  Bioinformatician
macromolecularnanomachines
IN ACTION
Sequence
   Structure
Sequence
   Structure
       Function
10 nm




100 nm




1 mm
X-Ray Diffraction
Crystallography
conformational changes
Simian Virus 40
Large T antigen
Simian virus 40
(SV40)
Large T antigen
High       Middle     Long &     Short &
curvature   curvature   straight   straight
High       Middle     Long &     Short &
curvature   curvature   straight   straight
Bacteriophage SPP1 replicative
         Helicase G40P
D. melanogaster
26S proteasome
26S proteasome
X-Ray               High       Requires
Crystallography      Resolution   Crystals   
X-Ray               High       Requires
Crystallography      Resolution   Crystals     

 3D Electron          Crystals      Medium
 Microscopy        Not required   Resolution   
X-Ray               High       Requires
Crystallography      Resolution   Crystals     

 3D Electron          Crystals      Medium
 Microscopy        Not required   Resolution   
X-Ray               High       Requires
Crystallography      Resolution   Crystals     

 3D Electron          Crystals      Medium
 Microscopy        Not required   Resolution   
X-Ray               High       Requires
Crystallography      Resolution   Crystals     

 3D Electron          Crystals      Medium
 Microscopy        Not required   Resolution   


                          Hybrid Models
X-Ray               High         Requires
Crystallography      Resolution     Crystals     

 3D Electron          Crystals        Medium
 Microscopy        Not required     Resolution   
                               Fitting



                          Hybrid Models
3D-EM model   Atomic model
Hybrid model
GroEL chaperonin
Anti-tumoral
P53 transcription factor
Electron
 Microscopy
      Data
         Bank
363

“since June 2002, the number
 of structures has increased
 steadily.”                           266



                               193




                        117


                 67
         40
 10


2002    2003    2004   2005    2006   2007   2008
Today there are
                                     629 entries




 Single
Particle   Icosahedral
                         Helical
                                    Individual
                                    Structure    2D Crystal
1 out of 3 structures
      are covered by more than
      one entry




369
DASx3DEM & PeppeR
http://biocomp.cnb.csic.es/das/PeppeR
Sequence
   Structure
adopting different conformations
                  is what leads to function

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Macromolecular Nanomachines In Action