GroELGroES Chaperonin Complex PDB ID 1AON

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GroEL-GroES Chaperonin ComplexPDB ID 1AON
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What are Chaperonins?

• Large double-ring-shaped protein complexes
• whose role in vivo is to assist protein folding

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Where can chaperonins be found?

• Classified by Sequence Homology
• Group I     (GroES dependent) GroEL       
  eubacteria Hsp60        mitochondria  
    Rubisco      chloroplasts
• Group II    (GroES independent) thermosome/TF
  55     archaea TCP1/CCT              
  eukaryotic

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Causes of Aggregations

• Hydrophobic Interactions
• Interchain hydrogen bonding
• Intracellular Crowding
• U Unfolded protein chain
• N Native fold protein
• I partially folded Intermediate

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Consequences of Aggregation

• Amyloid results from Structured fibrillar
  aggregates
• Associated Diseases    Alzheimer's   
  Huntington's

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Chaperonins counteract non-native protein
aggregation

• During de novo folding Under Stress (e.g. high
  temperature)

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Experimental Details

• Method
• X-Ray Diffraction
• Resolution
• 3A
• R-Factor
• 24.8
• Crystal Unit Cell Dimensions
• dim Å a 255.26 b 265.25 c 184.40
• angles alpha90.00 beta 90.00 gamma 90.00
• Space Group
• P21212

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GroEL-GroES ArchitectureE E. coli

• GroES
• S Small One heptameric ring 7 identical 10kD
  subunits
• Chains O-U
• GroELL Large
• Two heptameric rings stacked back to back 14
  identical 57kD subunits
• Chains A-N

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GroEL-GroES Architecture
Polar Charge blue Hydrophobic
yellow Backbone white Solvent-Excluded surfaces
gray
Equatorial pink Intermediate yellow Apical
blue
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GroES-GroEL Dimensions
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GroEL-GroES Sequences8337 Residues 58884 Atoms
Equatorial orange Intermediate purple
Apical cyan
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GroES Domain

• CATH
• Mainly Beta Roll

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GroEL Domains

• CATH
• Equatorial
• Mainly Alpha Orthogonal Bundle
• Intermediate
• Alpha Beta 2-Layer Sandwich
• Apical
• 3-Layer(bba) Sandwich

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GroES Mobile Loop
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GroEL Domains
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GroEL-GroES Binding Sites
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Conformational Change
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Conformational Change
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Conformational Change of Cavity
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Conformational Change
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How do chaperonins work?

• Bind non-native polypeptide through hydrophobic
  interaction
• Allow non-native polypeptide to fold in an
  isolated hydrophobic environment

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Overall Chaperonins Protein Folding Reaction

• 1. Non-native polypeptide bind to trans ring of
  GroEL2. 7ATP (equatorial) and GroES bind cis
  ring of GroEL2. Dissociation of 7ADP and GroES
  from from cis ring of GroEL3. Apical domain of
  GroEL undergo massive rotation and upward
  movement enlarging the cavity by 2X and shifting
  its surface properties from hydropobic to
  hydrophilic

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• E. Coli have 4300 proteins
• 13 are 55kD (500 residues)
• 10 polypeptides transit
• GroEL-GroES complex
• 3uM cytosolic concentration of GroEL
• 30uM ribosomes
• ½ life of 20-60 kD folded proteins 15sec to few
  mins

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1A6E Thermosome - Mg-ADP-Alf3 Complex 1A6D
Thermosome From T. Acidophilum
1AON chain A red 1A6E chain A yellow
1A6D chain A green
Ca 4.15A 87 atoms
Ca 4.58 A 87 atoms
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Structural Neighbors

• Criteria used
• 1AON chain A
• Z-Scoregt4.0
• RMSDlt4.0Å
• Length Differencelt30.0
• Gapslt30.0
• Sequence identitylt30.0

• Found used 1BPWA
• Z-Score 4.2
• RMSD(Å) 3.8
• Seq.() 2.3
• Aligned / Size 88 / 503
• Gap 25
• Exp X-Ray

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ALDEHYDE DEHYDROGENASE(CHAIN A) PDB ID 1BPW