4z2z | pdb_00004z2z
New crystal structure of yeast Ddi1 aspartyl protease reveals substrate engagement mode
Structural highlights
Function[DDI1_YEAST] Acts as a linker between the 19S proteasome and polyubiquitinated proteins like the HO endonuclease and UFO1 via UBA domain interactions with ubiquitin for their subsequent degradation. Required for S-phase checkpoint control. Appears to act as negative regulator of constitutive exocytosis. May act at the level of secretory vesicle docking and fusion as a competitive inhibitor of SNARE assembly.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedThe eukaryotic Ddi1 family is defined by a conserved retroviral aspartyl protease-like (RVP) domain found in association with a ubiquitin-like (UBL) domain. Ddi1 from Saccharomyces cerevisiae additionally contains a ubiquitin-associated (UBA) domain. The substrate specificity and role of the protease domain in the biological functions of the Ddi family remain unclear. Yeast Ddi1 has been implicated in the regulation of cell cycle progression, DNA-damage repair, and exocytosis. Here, we investigated the multi-domain structure of yeast Ddi1 using X-ray crystallography, nuclear magnetic resonance, and small-angle X-ray scattering. The crystal structure of the RVP domain sheds light on a putative substrate recognition site involving a conserved loop. Isothermal titration calorimetry confirms that both UBL and UBA domains bind ubiquitin, and that Ddi1 binds K48-linked diubiquitin with enhanced affinity. The solution NMR structure of a helical domain that precedes the protease displays tertiary structure similarity to DNA-binding domains from transcription regulators. Our structural studies suggest that the helical domain could serve as a landing platform for substrates in conjunction with attached ubiquitin chains binding to the UBL and UBA domains. Structural studies of the yeast DNA damage-inducible protein Ddi1 reveal domain architecture of this eukaryotic protein family.,Trempe JF, Saskova KG, Siva M, Ratcliffe CD, Veverka V, Hoegl A, Menade M, Feng X, Shenker S, Svoboda M, Kozisek M, Konvalinka J, Gehring K Sci Rep. 2016 Sep 20;6:33671. doi: 10.1038/srep33671. PMID:27646017[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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