Structural analysis of UBL5, a novel ubiquitin-like modifier.
UBL5 is a widely expressed human protein that is strongly conserved across phylogeny. Orthologs of UBL5 occur in every eukaryotic genome characterized to date. The yeast ortholog of UBL5, HUB1, was reported to be a ubiquitin-like protein modifier important for modulation of protein function. However, unlike ubiquitin and all other ubiquitin-like modifiers, UBL5 and its yeast ortholog HUB1 both contain a C-terminal di-tyrosine motif followed by a single variable residue instead of the characteristic di-glycine found in all other ubiquitin-like modifiers. Here we describe the three-dimensional structure of UBL5 determined by NMR. The overall structure of the protein was found to be very similar to ubiquitin despite the low approximately 25% residue similarity. The signature C-terminal di-tyrosine residues in UBL5 are involved in the final beta sheet of the protein. This is very different to the di-glycine motif found in ubiquitin, which extends beyond the final beta sheet. In addition, we have confirmed an earlier report of an interaction between UBL5 and the cyclin-like kinase, CLK4, which we have determined is specific and does not extend to other cyclin-like kinase family members.
McNally
Teresa
T
Global Pharmaceutical Research and Discovery, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA.
Huang
Qiulong
Q
Janis
Richard S
RS
Liu
Zhihong
Z
Olejniczak
Edward T
ET
Reilly
Regina M
RM
D000595:Amino Acid Sequence; D018844:Cyclin-Dependent Kinases / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005136:Eye Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005998:Glycine / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D017510:Protein Folding; D016415:Sequence Alignment; D020798:Two-Hybrid System Techniques; D014443:Tyrosine / Q000737:chemistry; D014452:Ubiquitins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D005136:Eye Proteins; C429294:UBL5 protein, human; D014452:Ubiquitins; D014443:Tyrosine; D018844:Cyclin-Dependent Kinases; D005998:Glycine