Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2

Structure. 2004 Dec;12(12):2257-63. doi: 10.1016/j.str.2004.10.007.


The caspase-associated ring proteins (CARP1 and CARP2) are distinguished from other caspase regulators by the presence of a FYVE-type zinc finger domain. FYVE-type domains are divided into two known classes: FYVE domains that specifically bind to phosphatidylinositol 3-phosphate in lipid bilayers and FYVE-related domains of undetermined function. Here, we report the crystal structure of the N-terminal region of CARP2 (44-139) including the FYVE-type domain and its associated helical bundle at 1.7 A resolution. The structure reveals a cramped phosphoinositide binding pocket and a blunted membrane insertion loop. These structural features indicate that the domain is not optimized to bind to phosphoinositides or insert into lipid bilayers. The CARP2 FYVE-like domain thus defines a third subfamily of FYVE-type domains that are functionally and structurally distinct. Structural analyses provide insights into the possible function of this unique subfamily of FYVE-type domains.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis Regulatory Proteins
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins
  • Cell Membrane / metabolism
  • Crystallization
  • Humans
  • Ligands
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins
  • Phosphatidylinositols / metabolism
  • Protein Structure, Tertiary
  • Zinc Fingers*


  • Apoptosis Regulatory Proteins
  • CA11 protein, human
  • CCAR1 protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • Ligands
  • Nerve Tissue Proteins
  • Phosphatidylinositols

Associated data

  • PDB/1Y02