Pfam

Using FASTA-formatted protein sequence for NLRP1 isoform 5, protein domains were obtained from Pfam[1]. 3 significant matches and 1 insignificant match were generated. The PAAD/DAPIN/Pyrin domain corresponds to the green domain on the figure below. The NACHT domain corresponds to the red domain while the LRR_1 repeat domain corresponds to the blue domain. 

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NLRP1 Domains: PAAD DAPIN (Green); NACHT (Red); LRR_1 (Blue)

PAAD DAPIN (PYD)

PAAD DAPIN Domain Structure

According to Pfam[1], this domain is predicted to contain 6 alpha helices and to have the same fold as the death domain, suggesting that the PAAD DAPIN domain may be a protein-protein interaction domain.

Pyrin domain was identified as putative protein-protein interaction domain at the N-terminal region of several proteins thought to function in apoptotic and inflammatory signalling pathways. This domain is believed to belong to a superfamily of domains that include death domains (DDs), death effector domains (DEDs), and caspase recruitment domains (CARDs). Members of the death domain-fold superfamily are well established mediators of protein-protein interactions found in many proteins involved in apoptosis and inflammation. 

When the NLRP1 protein is activated (via microbial MDP, or constitutively when NRLP1 is mutated), the PYD domain on the protein binds a PYD-CARD domain. The CARD domain of this protein, in turn, binds to the CARD domain on Caspase 1, thus signalling a caspase cascade to signal apoptosis. See figure below. 

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NACHT 

NACHT HMM Logo

The NACHT domain is a nucleoside triphosphatase (NTPase) domain. It is found in association with other domains, such as the CARD domain, the DAPIN domain, [...] and the leucine-rich repeat (LRR), domains observed on the NLRP1 gene. 

The NACHT domain consists of seven distinct conserved motifs, among them the ATP/GTPase specific P-loop and the Mg(2+)-binding site.

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nacht_domain_logo.png
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LRR_1

Leucine Rich Repeat 1

Leucine Rich Repeats consist of a beta-alpha unit. These units generally form non-globular structures and are often flanked by cysteine rich domains. The leucine rich repeats are responsible for binding the microbial invaders that normally stimulate an immune response. 

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NLRP1 Protein - Active Conformation

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cardfastadomain.txt
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References

[1] Pfam: http://pfam.sanger.ac.uk/




This Web site was created as a project for Genetics 677, Spring 2010.


May 16, 2010. Sarah Hamilton.