Title

Multivalent endosome targeting by homodimeric EEA1

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Molecular Medicine and Department of Biochemistry and Molecular Pharmacology

Date

12-14-2001

Document Type

Article

Medical Subject Headings

Amino Acid Sequence; Autoantigens; Crystallography, X-Ray; Dimerization; Endosomes; Inositol Phosphates; Membrane Proteins; Models, Biological; Models, Molecular; Molecular Sequence Data; Phospholipids; Protein Binding; *Protein Structure, Quaternary; Protein Structure, Tertiary; Sequence Alignment; Vesicular Transport Proteins; Zinc Fingers; rab5 GTP-Binding Proteins

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Early endosome autoantigen localization to early endosomes is mediated by a C-terminal region, which includes a calmodulin binding motif, a Rab5 interaction site, and a FYVE domain that selectively binds phosphatidyl inositol 3-phosphate. The crystal structure of the C-terminal region bound to inositol 1,3-bisphosphate reveals an organized, quaternary assembly consisting of a parallel coiled coil and a dyad-symmetric FYVE domain homodimer. Structural and biochemical observations support a multivalent mechanism for endosomal localization in which domain organization, dimerization, and quaternary structure amplify the weak affinity and modest specificity of head group interactions with conserved residues. A unique mode of membrane engagement deduced from the quaternary structure of the C-terminal region provides insight into the structural basis of endosome tethering.

Rights and Permissions

Citation: Mol Cell. 2001 Nov;8(5):947-58.

Related Resources

Link to article in PubMed

PubMed ID

11741531