5JUY

Active human apoptosome with procaspase-9


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.10 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

A near atomic structure of the active human apoptosome.

Cheng, T.C.Hong, C.Akey, I.V.Yuan, S.Akey, C.W.

(2016) Elife 5

  • DOI: https://doi.org/10.7554/eLife.17755
  • Primary Citation of Related Structures:  
    5JUY

  • PubMed Abstract: 

    In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). Here we report a near atomic structure of the active human apoptosome determined by cryo-electron microscopy. The resulting model gives insights into cytochrome c binding, nucleotide exchange and conformational changes that drive assembly. During activation an acentric disk is formed on the central hub of the apoptosome. This disk contains four Apaf-1/pc-9 CARD pairs arranged in a shallow spiral with the fourth pc-9 CARD at lower occupancy. On average, Apaf-1 CARDs recruit 3 to 5 pc-9 molecules to the apoptosome and one catalytic domain may be parked on the hub, when an odd number of zymogens are bound. This suggests a stoichiometry of one or at most, two pc-9 dimers per active apoptosome. Thus, our structure provides a molecular framework to understand the role of the apoptosome in programmed cell death and disease.


  • Organizational Affiliation

    Department of Physiology and Biophysics, Boston University School of Medicine, Boston, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Apoptotic protease-activating factor 1
A, B, C, D, E
A, B, C, D, E, F, G
1,248Homo sapiensMutation(s): 0 
Gene Names: APAF1KIAA0413
UniProt & NIH Common Fund Data Resources
Find proteins for O14727 (Homo sapiens)
Explore O14727 
Go to UniProtKB:  O14727
PHAROS:  O14727
GTEx:  ENSG00000120868 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO14727
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Cytochrome c
H, I, J, K, L
H, I, J, K, L, M, N
104Bos taurusMutation(s): 0 
UniProt
Find proteins for P62894 (Bos taurus)
Explore P62894 
Go to UniProtKB:  P62894
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP62894
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Caspase-9
O, P, Q, R
95Homo sapiensMutation(s): 0 
Gene Names: CASP9MCH6
EC: 3.4.22.62
UniProt & NIH Common Fund Data Resources
Find proteins for P55211 (Homo sapiens)
Explore P55211 
Go to UniProtKB:  P55211
PHAROS:  P55211
GTEx:  ENSG00000132906 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP55211
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
HEC
Query on HEC

Download Ideal Coordinates CCD File 
AA [auth I]
BA [auth J]
CA [auth K]
DA [auth L]
EA [auth M]
AA [auth I],
BA [auth J],
CA [auth K],
DA [auth L],
EA [auth M],
FA [auth N],
Z [auth H]
HEME C
C34 H34 Fe N4 O4
HXQIYSLZKNYNMH-LJNAALQVSA-N
DTP
Query on DTP

Download Ideal Coordinates CCD File 
S [auth A]
T [auth B]
U [auth C]
V [auth D]
W [auth E]
S [auth A],
T [auth B],
U [auth C],
V [auth D],
W [auth E],
X [auth F],
Y [auth G]
2'-DEOXYADENOSINE 5'-TRIPHOSPHATE
C10 H16 N5 O12 P3
SUYVUBYJARFZHO-RRKCRQDMSA-N
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 4.10 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONRELION1.4
MODEL REFINEMENTPHENIX

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesRO1 GM63834

Revision History  (Full details and data files)

  • Version 1.0: 2016-10-19
    Type: Initial release
  • Version 1.1: 2016-10-26
    Changes: Other
  • Version 1.2: 2017-09-27
    Changes: Author supporting evidence
  • Version 1.3: 2018-07-18
    Changes: Data collection, Experimental preparation
  • Version 1.4: 2019-12-25
    Changes: Author supporting evidence