2c7n: Difference between revisions

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==Overview==
==Overview==
The interaction between ubiquitinated proteins and intracellular proteins, harboring ubiquitin binding domains (UBDs) is critical to a multitude of, cellular processes. Here, we report that Rabex-5, a guanine nucleotide, exchange factor for Rab5, binds to Ub through two independent UBDs. These, UBDs determine a number of properties of Rabex-5, including its coupled, monoubiquitination and interaction in vivo with ubiquitinated EGFRs., Structural and biochemical characterization of the UBDs of Rabex-5, revealed that one of them (MIU, motif interacting with ubiquitin) binds to, Ub with modes superimposable to those of the UIM (ubiquitin-interacting, motif):Ub interaction, although in the opposite orientation. The other, UBD, RUZ (Rabex-5 ubiquitin binding zinc finger) binds to a surface of Ub, centered on Asp58(Ub) and distinct from the "canonical" Ile44(Ub)-based, surface. The two binding surfaces allow Ub to interact simultaneously with, different UBDs, thus opening new perspectives in Ub-mediated signaling.
The interaction between ubiquitinated proteins and intracellular proteins harboring ubiquitin binding domains (UBDs) is critical to a multitude of cellular processes. Here, we report that Rabex-5, a guanine nucleotide exchange factor for Rab5, binds to Ub through two independent UBDs. These UBDs determine a number of properties of Rabex-5, including its coupled monoubiquitination and interaction in vivo with ubiquitinated EGFRs. Structural and biochemical characterization of the UBDs of Rabex-5 revealed that one of them (MIU, motif interacting with ubiquitin) binds to Ub with modes superimposable to those of the UIM (ubiquitin-interacting motif):Ub interaction, although in the opposite orientation. The other UBD, RUZ (Rabex-5 ubiquitin binding zinc finger) binds to a surface of Ub centered on Asp58(Ub) and distinct from the "canonical" Ile44(Ub)-based surface. The two binding surfaces allow Ub to interact simultaneously with different UBDs, thus opening new perspectives in Ub-mediated signaling.


==About this Structure==
==About this Structure==
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[[Category: Protein complex]]
[[Category: Protein complex]]
[[Category: Confalioneri, S.]]
[[Category: Confalioneri, S.]]
[[Category: Fiore, P.P.Di.]]
[[Category: Fiore, P P.Di.]]
[[Category: Magri, L.]]
[[Category: Magri, L.]]
[[Category: Mapelli, M.]]
[[Category: Mapelli, M.]]
[[Category: Murachelli, A.G.]]
[[Category: Murachelli, A G.]]
[[Category: Musacchio, A.]]
[[Category: Musacchio, A.]]
[[Category: Penengo, L.]]
[[Category: Penengo, L.]]
[[Category: Polo, S.]]
[[Category: Polo, S.]]
[[Category: Schneider, T.R.]]
[[Category: Schneider, T R.]]
[[Category: ZN]]
[[Category: ZN]]
[[Category: endocytosis]]
[[Category: endocytosis]]
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[[Category: ubl conjugation]]
[[Category: ubl conjugation]]


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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:45:46 2008''

Revision as of 17:45, 21 February 2008

File:2c7n.gif


2c7n, resolution 2.10Å

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HUMAN RABEX-5 RESIDUES 1-74 IN COMPLEX WITH UBIQUITIN

OverviewOverview

The interaction between ubiquitinated proteins and intracellular proteins harboring ubiquitin binding domains (UBDs) is critical to a multitude of cellular processes. Here, we report that Rabex-5, a guanine nucleotide exchange factor for Rab5, binds to Ub through two independent UBDs. These UBDs determine a number of properties of Rabex-5, including its coupled monoubiquitination and interaction in vivo with ubiquitinated EGFRs. Structural and biochemical characterization of the UBDs of Rabex-5 revealed that one of them (MIU, motif interacting with ubiquitin) binds to Ub with modes superimposable to those of the UIM (ubiquitin-interacting motif):Ub interaction, although in the opposite orientation. The other UBD, RUZ (Rabex-5 ubiquitin binding zinc finger) binds to a surface of Ub centered on Asp58(Ub) and distinct from the "canonical" Ile44(Ub)-based surface. The two binding surfaces allow Ub to interact simultaneously with different UBDs, thus opening new perspectives in Ub-mediated signaling.

About this StructureAbout this Structure

2C7N is a Protein complex structure of sequences from Homo sapiens with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin., Penengo L, Mapelli M, Murachelli AG, Confalonieri S, Magri L, Musacchio A, Di Fiore PP, Polo S, Schneider TR, Cell. 2006 Mar 24;124(6):1183-95. Epub 2006 Feb 23. PMID:16499958

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