Solution structure of the Kaposi's sarcoma-associated herpesvirus K3 N-terminal domain reveals a Novel E2-binding C4HC3-type RING domain.
RING domains are found in a large number of eukaryotic proteins. Most function as E3 ubiquitin-protein ligases, catalyzing the terminal step in the ubiquitination process. Structurally, these domains have been characterized as binding two zinc ions in a stable cross-brace motif. The tumorigenic human gamma-herpesvirus Kaposi's sarcoma-associated herpesvirus encodes a ubiquitin-protein ligase termed K3, which functions as an immune evasion molecule by ubiquitinating major histocompatibility complex class I. K3 possesses at its N terminus a domain related to cellular RING domains but with an altered zinc ligand arrangement. This domain was initially characterized as a plant homeodomain, a structure not previously known to function as an E3. Here, it is conclusively demonstrated that the K3 N-terminal domain is a variant member of the RING domain family and not a plant homeodomain. The domain is found to interact with the cellular ubiquitin-conjugating enzymes UbcH5A to -C and UbcH13, which dock to the equivalent surface as on classical cellular RING domains. Interaction with UbcH13 suggests a possible role for K3 in catalyzing Lys(63)-linked ubiquitination.
Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK.
Roger B
RB
Dodd
Mark D
MD
Allen
Stephanie E
SE
Brown
Christopher M
CM
Sanderson
Lidia M
LM
Duncan
Paul J
PJ
Lehner
Mark
M
Bycroft
Randy J
RJ
Read
D000595:Amino Acid Sequence; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D014364:Tryptophan / Q000737:chemistry; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000737:chemistry; D014764:Viral Proteins / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry
C456022:K3 protein, Kaposi's sarcoma-associated herpesvirus; D025801:Ubiquitin; D014764:Viral Proteins; D014364:Tryptophan; D015032:Zinc