GSBS Student Publications

Title

Evolutionarily conserved structural and functional roles of the FYVE domain

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Program in Molecular Medicine

Date

1-20-2007

Document Type

Article

Medical Subject Headings

Amino Acid Motifs; Amino Acid Sequence; Animals; Endosomes; *Evolution, Molecular; Green Fluorescent Proteins; Humans; Intracellular Signaling Peptides and Proteins; Molecular Sequence Data; Phosphatidylinositol Phosphates; Protein Structure, Tertiary; Sensitivity and Specificity; Sequence Homology, Amino Acid

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The FYVE domain is an approx. 80 amino acid motif that binds to the phosphoinositide PtdIns3P with high specificity and affinity. It is present in 38 predicted gene products within the human genome, but only in 12-13 in Caenorhabditis elegans and Drosophila melanogaster. Eight of these are highly conserved in all three organisms, and they include proteins that have not been characterized in any species. One of these, WDFY2, appears to play an important role in early endocytosis and was revealed in a RNAi (RNA interference) screen in C. elegans. Interestingly, some proteins contain FYVE-like domains in C. elegans and D. melanogaster, but have lost this domain during evolution. One of these is the homologue of Rabatin-5, a protein that, in mammalian cells, binds both Rab5 and Rabex-5, a guanine-nucleotide exchange factor for Rab5. Thus the Rabatin-5 homologue suggests that mechanisms to link PtdIns3P and Rab5 activation developed in evolution. In mammalian cells, these mechanisms are apparent in the existence of proteins that bind PtdIns3P and Rab GTPases, such as EEA1, Rabenosyn-5 and Rabip4'. Despite the comparable ability to bind to PtdIns3P in vitro, FYVE domains display widely variable abilities to interact with endosomes in intact cells. This variation is due to three distinct properties of FYVE domains conferred by residues that are not involved in PtdIns3P head group recognition: These properties are: (i) the propensity to oligomerize, (ii) the ability to insert into the membrane bilayer, and (iii) differing electrostatic interactions with the bilayer surface. The different binding properties are likely to regulate the extent and duration of the interaction of specific FYVE domain-containing proteins with early endosomes, and thereby their biological function.

Rights and Permissions

Citation: Biochem Soc Symp. 2007;(74):95-105. Link to article on publisher's site

DOI of Published Version

10.1042/BSS0740095

Related Resources

Link to article in PubMed

Journal Title

Biochemical Society symposium

PubMed ID

17233583