Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of ''C. elegans'' CED-4 gene.
Function
The protein was identified in the lab of
Xiaodong Wang as an activator of caspase-3 in the presense of cytochromeC and dATP.
This gene encodes a cytoplasmic protein that forms one of the central hubs in the
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
regulatory network. This protein contains (from the N terminal) a caspase recruitment domain (
CARD Card or The Card may refer to:
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), an
ATPase
ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are ...
domain (NB-ARC), few short helical domains and then several copies of the
WD40 repeat
The WD40 repeat (also known as the WD or beta-transducin repeat) is a short structural motif of approximately 40 amino acids, often terminating in a tryptophan-aspartic acid (W-D) dipeptide. Tandem copies of these repeats typically fold togethe ...
domain. Upon binding
cytochrome c
The cytochrome complex, or cyt ''c'', is a small hemeprotein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins and plays a major role in cell apoptosis. Cytochrome c is hig ...
and
dATP
Deoxyadenosine triphosphate (dATP) is a nucleotide used in cells for DNA synthesis (or replication), as a substrate of DNA polymerase. It is classified as a purine nucleoside triphosphate, with its chemical structure consisting of a deoxyribose s ...
, this protein forms an oligomeric
apoptosome
The apoptosome is a large quaternary protein structure formed in the process of apoptosis. Its formation is triggered by the release of cytochrome c from the mitochondria in response to an internal (intrinsic) or external (extrinsic) cell death st ...
. The apoptosome binds and cleaves
Procaspase-9 protein, releasing its mature, activated form. The precise mechanism for this reaction is still debated though work published by
Guy Salvesen
Guy Salvesen is a South African-born biochemist, best known for his work in the field of apoptosis. His research focuses on proteases and their inhibitors in humans, with particular emphasis on the caspases of the apoptotic cell death pathway.
Hi ...
suggests that the apoptosome may induce
caspase-9
Caspase-9 is an enzyme that in humans is encoded by the CASP9 gene. It is an initiator caspase, critical to the apoptotic pathway found in many tissues. Caspase-9 homologs have been identified in all mammals for which they are known to exist, such ...
dimerization and subsequent
autocatalysis
A single chemical reaction is said to be autocatalytic if one of the reaction products is also a catalyst for the same or a coupled reaction.Steinfeld J.I., Francisco J.S. and Hase W.L. ''Chemical Kinetics and Dynamics'' (2nd ed., Prentice-Hall 199 ...
.
Activated caspase-9 stimulates the subsequent caspase cascade that commits the cell to apoptosis.
Alternative splicing
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be ...
results in several transcript variants encoding different isoforms.
Structure
APAF1 contains a
CARD domain
Caspase recruitment domains, or caspase activation and recruitment domains (CARDs), are interaction motifs found in a wide array of proteins, typically those involved in processes relating to inflammation and apoptosis. These domains mediate th ...
with a
Greek key motif composed of six helices, a Rossman fold nucleotide binding domains, a short helical motif and a winged-helix domain.
![177-Apoptosomes human apoptosome](https://upload.wikimedia.org/wikipedia/commons/3/37/177-Apoptosomes_human_apoptosome.png)
Interactions
APAF1 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
*
APIP
APAF1-interacting protein is a protein that in humans is encoded by the ''APIP'' gene. It is an enzyme with Methylthioribulose 1-phosphate dehydratase activity which is involved in the methionine salvage pathway.
APIP deficiency is associated wi ...
,
[
* BCL2-like 1][
* ]Caspase-9
Caspase-9 is an enzyme that in humans is encoded by the CASP9 gene. It is an initiator caspase, critical to the apoptotic pathway found in many tissues. Caspase-9 homologs have been identified in all mammals for which they are known to exist, such ...
,
* HSPA4
Heat shock 70 kDa protein 4 is a protein that in humans is encoded by the ''HSPA4'' gene.
The protein encoded by this gene was originally suggested to be a member of the heat shock protein 70 family. However it is now known that human HSPA4 is a ...
, and
* NLRP1
NLRP1 encodes NACHT, LRR, FIIND, CARD domain and PYD domains-containing protein 1 in humans. NLRP1 was the first protein shown to form an inflammasome. Material was copied from this source, which is available under Creative Commons Attribution 4. ...
.
References
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{{DEFAULTSORT:Apaf1
Programmed cell death
Apoptosis