Mechanism of Aldolase Control of Sorting Nexin 9 Function in Endocytosis

Journal Article · Wed Nov 03 04:00:00 EDT 2010 · J. Biol. Chem.

DOI:https://doi.org/10.1074/jbc.M109.092049· OSTI ID:1002408

Rangarajan, Erumbi S; Park, HaJeung; Fortin, Emanuelle; Sygusch, Jurgen; Izard, Tina ^[1]

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1. Scripps

Sorting nexin 9 (SNX9) functions in a complex with the GTPase dynamin-2 at clathrin-coated pits, where it provokes fission of vesicles to complete endocytosis. Here the SNX9-dynamin-2 complex binds to clathrin and adapter protein complex 2 (AP-2) that line these pits, and this occurs through interactions of the low complexity domain (LC4) of SNX9 with AP-2. Intriguingly, localization of the SNX9-dynamin-2 complex to clathrin-coated pits is blocked by interactions with the abundant glycolytic enzyme aldolase, which also binds to the LC4 domain of SNX9. The crystal structure of the LC4 motif of human SNX9 in complex with aldolase explains the biochemistry and biology of this interaction, where SNX9 binds near the active site of aldolase via residues 165-171 that are also required for the interactions of SNX9 with AP-2. Accordingly, SNX9 binding to aldolase is structurally precluded by the binding of substrate to the active site. Interactions of SNX9 with aldolase are far more extensive and differ from those of the actin-nucleating factor WASP with aldolase, indicating considerable plasticity in mechanisms that direct the functions of the aldolase as a scaffold protein.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1002408
• Journal Information: J. Biol. Chem., Journal Name: J. Biol. Chem. Journal Issue: (16) ; 04, 2010 Vol. 285; ISSN JBCHA3; ISSN 0021-9258
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
ALDOLASES
BIOCHEMISTRY
BIOLOGY
CRYSTAL STRUCTURE
ENZYMES
FISSION
PLASTICITY
PROTEINS
RESIDUES
SORTING
SUBSTRATES
WASPS