title: Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2.
abstract: 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.
authors.affiliation: Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Tibbetts
authors.forename: Eric N
authors.initials: EN
authors.lastname: Shiozaki
authors.forename: Lichuan
authors.initials: L
authors.lastname: Gu
authors.forename: E Robert
authors.initials: ER
authors.lastname: McDonald
authors.forename: Wafik S
authors.initials: WS
authors.lastname: El-Deiry
authors.forename: Yigong
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D002462:Cell Membrane / Q000378:metabolism; D003460:Crystallization; D006801:Humans; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D010716:Phosphatidylinositols / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016335:Zinc Fingers
chemical_list: D051017:Apoptosis Regulatory Proteins; C512817:CA11 protein, human; C477529:CCAR1 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D008024:Ligands; D009419:Nerve Tissue Proteins; D010716:Phosphatidylinositols