1q5w: Difference between revisions
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New page: left|200px<br /> <applet load="1q5w" size="450" color="white" frame="true" align="right" spinBox="true" caption="1q5w" /> '''Ubiquitin Recognition by Npl4 Zinc-Fingers'... |
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[[Image:1q5w. | [[Image:1q5w.jpg|left|200px]]<br /><applet load="1q5w" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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'''Ubiquitin Recognition by Npl4 Zinc-Fingers'''<br /> | '''Ubiquitin Recognition by Npl4 Zinc-Fingers'''<br /> | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191339 191339]] | |||
==About this Structure== | ==About this Structure== | ||
1Q5W is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1Q5W is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q5W OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: zinc-finger]] | [[Category: zinc-finger]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:42:51 2008'' | ||
