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Title: Structural Basis for Ubiquitin Recognition and Autoubiquitination by Rabex-5

Abstract

Rabex-5 is an exchange factor for Rab5, a master regulator of endosomal trafficking. Rabex-5 binds monoubiquitin, undergoes covalent ubiquitination and contains an intrinsic ubiquitin ligase activity, all of which require an N-terminal A20 zinc finger followed immediately by a helix. The structure of the N-terminal portion of Rabex-5 bound to ubiquitin at 2.5-Angstroms resolution shows that Rabex-5-ubiquitin interactions occur at two sites. The first site is a new type of ubiquitin-binding domain, an inverted ubiquitin-interacting motif, which binds with {approx}29-{mu}M affinity to the canonical Ile44 hydrophobic patch on ubiquitin. The second is a diaromatic patch on the A20 zinc finger, which binds with {approx}22-{mu}M affinity to a polar region centered on Asp58 of ubiquitin. The A20 zinc-finger diaromatic patch mediates ubiquitin-ligase activity by directly recruiting a ubiquitin-loaded ubiquitin-conjugating enzyme.

Authors:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
914147
Report Number(s):
BNL-78715-2007-JA
TRN: US0801574
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nat. Struct. Mol. Biol.; Journal Volume: 13
Country of Publication:
United States
Language:
English
Subject:
43 PARTICLE ACCELERATORS; AFFINITY; FINGERS; LIGASES; POLAR REGIONS; RESOLUTION; ZINC; NSLS; national synchrotron light source

Citation Formats

Lee,S., Tsai, Y., Mattera, R., Smith, W., Kostelansky, M., Weissman, A., Bonifacino, J., and Hurley, J. Structural Basis for Ubiquitin Recognition and Autoubiquitination by Rabex-5. United States: N. p., 2006. Web. doi:10.1038/nsmb1064.
Lee,S., Tsai, Y., Mattera, R., Smith, W., Kostelansky, M., Weissman, A., Bonifacino, J., & Hurley, J. Structural Basis for Ubiquitin Recognition and Autoubiquitination by Rabex-5. United States. doi:10.1038/nsmb1064.
Lee,S., Tsai, Y., Mattera, R., Smith, W., Kostelansky, M., Weissman, A., Bonifacino, J., and Hurley, J. Sun . "Structural Basis for Ubiquitin Recognition and Autoubiquitination by Rabex-5". United States. doi:10.1038/nsmb1064.
@article{osti_914147,
title = {Structural Basis for Ubiquitin Recognition and Autoubiquitination by Rabex-5},
author = {Lee,S. and Tsai, Y. and Mattera, R. and Smith, W. and Kostelansky, M. and Weissman, A. and Bonifacino, J. and Hurley, J.},
abstractNote = {Rabex-5 is an exchange factor for Rab5, a master regulator of endosomal trafficking. Rabex-5 binds monoubiquitin, undergoes covalent ubiquitination and contains an intrinsic ubiquitin ligase activity, all of which require an N-terminal A20 zinc finger followed immediately by a helix. The structure of the N-terminal portion of Rabex-5 bound to ubiquitin at 2.5-Angstroms resolution shows that Rabex-5-ubiquitin interactions occur at two sites. The first site is a new type of ubiquitin-binding domain, an inverted ubiquitin-interacting motif, which binds with {approx}29-{mu}M affinity to the canonical Ile44 hydrophobic patch on ubiquitin. The second is a diaromatic patch on the A20 zinc finger, which binds with {approx}22-{mu}M affinity to a polar region centered on Asp58 of ubiquitin. The A20 zinc-finger diaromatic patch mediates ubiquitin-ligase activity by directly recruiting a ubiquitin-loaded ubiquitin-conjugating enzyme.},
doi = {10.1038/nsmb1064},
journal = {Nat. Struct. Mol. Biol.},
number = ,
volume = 13,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}