Structure of the NLRP1 caspase recruitment domain suggests potential mechanisms for its association with procaspase-1

Proteins. 2013 Jul;81(7):1266-70. doi: 10.1002/prot.24287. Epub 2013 Apr 20.

Abstract

The NLRP1 inflammasome responds to microbial challenges such as Bacillus anthracis infection and is implicated in autoimmune disease such as vitiligo. Human NLRP1 contains both an N-terminal pyrin domain (PYD) and a C-terminal caspase recruitment domain (CARD), with the latter being essential for its association with the downstream effector procaspase-1. Here we report a 2.0 Å crystal structure of the human NLRP1 CARD as a fusion with the maltose-binding protein. The structure reveals the six-helix bundle fold of the NLRP1 CARD, typical of the death domain superfamily. The charge surface of the NLRP1 CARD structure and a procaspase-1 CARD model suggests potential mechanisms for their association through electrostatic attraction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry*
  • Apoptosis Regulatory Proteins / chemistry*
  • Caspase 1 / chemistry*
  • Caspases / chemistry
  • Humans
  • Protein Binding*
  • Protein Interaction Maps
  • Protein Structure, Secondary
  • Protein Structure, Tertiary

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • NLRP1 protein, human
  • Caspases
  • Caspase 1