Caspases
What InterPro Tells Us
All caspases belong to one protein family, the peptidase C14 family, even though their domain architectures can vary. Below is an example from InterPro for human caspase-8, which carries two Death effector domains.
Q14790 Human Caspase-8 entry from InterPro
InterPro domain architecture
InterPro Entry |
Method accession |
Graphical match |
Method name |
|
IPR001309: |
PF00656
|
|
Peptidase_C14 |
|
IPR001309: |
PS01121 |
|
CASPASE_HIS |
|
IPR001309: |
PS01122 |
|
CASPASE_CYS |
|
IPR001309: |
PS50208 |
|
CASPASE_P20 |
|
IPR001875: |
PF01335 |
|
DED |
|
IPR001875: |
PS50168 |
|
DED |
|
IPR002138: |
PS50207 |
|
CASPASE_P10 |
|
IPR002398: |
PR00376 |
|
IL1BCENZYME |
|
IPR011029: |
SSF47986 |
|
DEATH_like |
Classification |
PBD Chain/Domain ID
|
PDB Chain/Structural Domains
|
|
|
1qtn |
1qtna |
|
|
|
1qtn |
1qtnb |
|
|
|
3.40.50.1460.1 |
1qtnA0 |
|
|
|
c.17.1.1 |
d1qtn.1 |
|
|
From the graphical match table above, you can see that the signatures (method accession) are divided into five InterPro entries for human caspase-8. These entries give information about the domain architecture of the protein, as well as its family relationships.
To look at the family relationships
that involve caspase-8, we need to look at the entry IPR002398, which has one
signature representing the peptidase C14 family (family 14 of the Cysteine
proteases): PR00376 from the PRINTS database.
The
domain architecture of caspase-8 is represented by the ‘InterPro domain architecture’
(IDA) diagram at the top of the page, as well as in the graphical match
table. The IDA diagram describes three
main domain types: (two) Death effector
domains (DED) involved in protein interactions, and p10 and p20 catalytic
domains. The Graphical match
table includes the signatures describing these domains. The two identical DED domains are represented
by IPR001875, which here has two
signatures: PF01335 from the PFAM database, and PS50168 from the PROSITE
database. The signature SSF47986 from the
SUPERFAMILY database also covers the DED domains; this entry represents the
Death-like domain IPR011029, which includes
the DED, Death and CARD domains, all of which show sequence homology to one
another.
The
caspase catalytic domain has two subunits, p10 and p20. The p20 domain is represented by IPR001309, which has four
signatures: PF00656 from the PFAM
database, which represents the entire catalytic domain (p20 and p10), PS01121, PS01122 and PS50208 from the PROSITE
database, all of which represent the p20 domain alone. The p10 domain is
represented by IPR002138, which has one
signature, PS50207 from the PROSITE
database.
The remaining entries in the table are from the structural database PDB, and from the structural classification databases CATH and SCOP, which display the regions of the protein that have structural information (the names such as 1qtna are derived from the PDB entry upon which they are based; here PDB entry 1qtn, chain a). The graphical matches for the PDB entries 1qtna and 1qtnb represent the caspase catalytic domains p20 and p10, respectively. The databases CATH and SCOP classify the PDB structures differently: CATH (1qtnA0) classifies the p20 catalytic domain alone, while SCOP (d1qtn.1) classifies the p20 and p10 subunits together as one structural unit.
What the Structure Tells Us
There are structures available for caspase-8, as well as for other caspases, in the Protein Data Bank (PDB). A detailed description and visualisation of the structural features of caspases can be found at the PDB 'Molecule of the Month'. The crystallographic structures of different caspases have provided insight into the catalytic action of these enzymes.