1q5w
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Ubiquitin (Ub) functions in many different biological pathways, where it | + | Ubiquitin (Ub) functions in many different biological pathways, where it typically interacts with proteins that contain modular Ub recognition domains. One such recognition domain is the Npl4 zinc finger (NZF), a compact zinc-binding module found in many proteins that function in Ub-dependent processes. We now report the solution structure of the NZF domain from Npl4 in complex with Ub. The structure reveals that three key NZF residues (13TF14/M25) surrounding the zinc coordination site bind the hydrophobic 'Ile44' surface of Ub. Mutations in the 13TF14/M25 motif inhibit Ub binding, and naturally occurring NZF domains that lack the motif do not bind Ub. However, substitution of the 13TF14/M25 motif into the nonbinding NZF domain from RanBP2 creates Ub-binding activity, demonstrating the versatility of the NZF scaffold. Finally, NZF mutations that inhibit Ub binding by the NZF domain of Vps36/ESCRT-II also inhibit sorting of ubiquitylated proteins into the yeast vacuole. Thus, the NZF is a versatile protein recognition domain that is used to bind ubiquitylated proteins during vacuolar protein sorting, and probably many other biological processes. |
==Disease== | ==Disease== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
| - | [[Category: Alam, S | + | [[Category: Alam, S L.]] |
| - | [[Category: Blake, B | + | [[Category: Blake, B K.]] |
| - | [[Category: Davis, D | + | [[Category: Davis, D R.]] |
| - | [[Category: Emr, S | + | [[Category: Emr, S D.]] |
| - | [[Category: Meyer, H | + | [[Category: Meyer, H H.]] |
[[Category: Payne, M.]] | [[Category: Payne, M.]] | ||
[[Category: Sun, J.]] | [[Category: Sun, J.]] | ||
| - | [[Category: Sundquist, W | + | [[Category: Sundquist, W I.]] |
| - | [[Category: Welch, B | + | [[Category: Welch, B D.]] |
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: nzf domain]] | [[Category: nzf domain]] | ||
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[[Category: zinc-finger]] | [[Category: zinc-finger]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:36:13 2008'' |
Revision as of 12:36, 21 February 2008
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Ubiquitin Recognition by Npl4 Zinc-Fingers
Contents |
Overview
Ubiquitin (Ub) functions in many different biological pathways, where it typically interacts with proteins that contain modular Ub recognition domains. One such recognition domain is the Npl4 zinc finger (NZF), a compact zinc-binding module found in many proteins that function in Ub-dependent processes. We now report the solution structure of the NZF domain from Npl4 in complex with Ub. The structure reveals that three key NZF residues (13TF14/M25) surrounding the zinc coordination site bind the hydrophobic 'Ile44' surface of Ub. Mutations in the 13TF14/M25 motif inhibit Ub binding, and naturally occurring NZF domains that lack the motif do not bind Ub. However, substitution of the 13TF14/M25 motif into the nonbinding NZF domain from RanBP2 creates Ub-binding activity, demonstrating the versatility of the NZF scaffold. Finally, NZF mutations that inhibit Ub binding by the NZF domain of Vps36/ESCRT-II also inhibit sorting of ubiquitylated proteins into the yeast vacuole. Thus, the NZF is a versatile protein recognition domain that is used to bind ubiquitylated proteins during vacuolar protein sorting, and probably many other biological processes.
Disease
Known disease associated with this structure: Cleft palate, isolated OMIM:[191339]
About this Structure
1Q5W is a Protein complex structure of sequences from Homo sapiens and Rattus norvegicus with as ligand. Full crystallographic information is available from OCA.
Reference
Ubiquitin interactions of NZF zinc fingers., Alam SL, Sun J, Payne M, Welch BD, Blake BK, Davis DR, Meyer HH, Emr SD, Sundquist WI, EMBO J. 2004 Apr 7;23(7):1411-21. Epub 2004 Mar 18. PMID:15029239
Page seeded by OCA on Thu Feb 21 14:36:13 2008
