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Ubiquitin interactions of NZF zinc fingers
Author(s) -
Alam Steven L,
Sun Ji,
Payne Marielle,
Welch Brett D,
Blake B Kelly,
Davis Darrell R,
Meyer Hemmo H,
Emr Scott D,
Sundquist Wesley I
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600114
Subject(s) - biology , escrt , zinc finger , ubiquitin , computational biology , vacuolar protein sorting , plasma protein binding , microbiology and biotechnology , biochemistry , mutant , gene , transcription factor , receptor , endosome
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 ( 13 TF 14 /M 25 ) surrounding the zinc coordination site bind the hydrophobic ‘Ile44’ surface of Ub. Mutations in the 13 TF 14 /M 25 motif inhibit Ub binding, and naturally occurring NZF domains that lack the motif do not bind Ub. However, substitution of the 13 TF 14 /M 25 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.