Ubiquitin is double-phosphorylated by PINK1 for enhanced pH-sensitivity of conformational switch
نویسندگان
چکیده
منابع مشابه
Ubiquitin S65 phosphorylation engenders a pH-sensitive conformational switch.
Ubiquitin (Ub) is an important signaling protein. Recent studies have shown that Ub can be enzymatically phosphorylated at S65, and that the resulting pUb exhibits two conformational states-a relaxed state and a retracted state. However, crystallization efforts have yielded only the structure for the relaxed state, which was found similar to that of unmodified Ub. Here we present the solution s...
متن کاملBinding to serine 65-phosphorylated ubiquitin primes Parkin for optimal PINK1-dependent phosphorylation and activation
Mutations in the mitochondrial protein kinase PINK1 are associated with autosomal recessive Parkinson disease (PD). We and other groups have reported that PINK1 activates Parkin E3 ligase activity both directly via phosphorylation of Parkin serine 65 (Ser(65))--which lies within its ubiquitin-like domain (Ubl)--and indirectly through phosphorylation of ubiquitin at Ser(65). How Ser(65)-phosphor...
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The human ubiquitin ligase HUWE1 has key roles in tumorigenesis, yet it is unkown how its activity is regulated. We present the crystal structure of a C-terminal part of HUWE1, including the catalytic domain, and reveal an asymmetric auto-inhibited dimer. We show that HUWE1 dimerizes in solution and self-associates in cells, and that both occurs through the crystallographic dimer interface. We ...
متن کاملPink1, the first ubiquitin kinase.
P ink1, a mitochondrial kinase, and Parkin, a cytosolic E3 ubiquitin ligase, function in mitochondrial maintenance. Pink1 is normally imported into mitochondria, cleaved by PARL protease, and degraded by the proteasome. When mitochondria lose their membrane potential, Pink1 starts to accumulate on the mitochondrial outer surface, where it recruits and activates Parkin to trigger protein ubiquit...
متن کاملAn invisible ubiquitin conformation is required for efficient phosphorylation by PINK1
The Ser/Thr protein kinase PINK1 phosphorylates the well-folded, globular protein ubiquitin (Ub) at a relatively protected site, Ser65. We previously showed that Ser65 phosphorylation results in a conformational change in which Ub adopts a dynamic equilibrium between the known, common Ub conformation and a distinct, second conformation wherein the last β-strand is retracted to extend the Ser65 ...
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ژورنال
عنوان ژورنال: Protein & Cell
سال: 2019
ISSN: 1674-800X,1674-8018
DOI: 10.1007/s13238-019-0644-x