Ubiquitination structure

Our results were in excellent agreement with d3mamic ensemble refinement of ubiquitin structures, showing that the native state of this protein must be considered a heterogeneous ensemble of conformations [38] which are sampled over a wide range of time scales [39]. 

Figure 17.1 In the protein quartet model [4], there are one ordered state and three intrinsically disordered states molten globular, premolten globular, and intrinsic coil. These states can exist under native conditions and interconvert. In the figure, the ordered protein is based on the structure of ubiquitin (PDB 1UBQ) [7], The other protein states are hypothetical models obtained by distorting the ubiquitin structure...

Pickart, C. M., and Eddins, M. J. (2004). Ubiquitin Structures, functions, mechanisms. Biochim et Biophys Acta (BBA) - Molecular Cell Research 1695, 55-72. 

An ensemble of ubiquitin structures based on RDC values found to comprise all different conformations that ubiquitin adopts upon binding to different recognition proteins. 

Di stefano D L and Wand A J 1987 Two-dimensional NMR study of human ubiquitin a main chain directed assignment and structure analysis Biochemistry 26 7272-81... 

Weber P L, Brown S 0 and Mueller L 1987 Sequential NMR assignment and secondary structure identification of human ubiquitin Biochemistry 26 7282-90... 

Adaptor Proteins. Figure 1 Adaptor protein domains. A scheme of the domain structures of some well-characterized adaptor proteins is shown. Descriptions of domain characteristics are in main text except C2, binds to phospholipids GTPase activating protein (GAP) domain, inactivates small GTPases such as Ras Hect domain, enzymatic domain of ubiquitin ligases and GUK domain, guanylate kinase domain. For clarity, not all domains contained within these proteins are shown. 

Chromatin is composed of nucleosomes, where each comprise 147 base pairs of DNA wrapped around an octamer oftwo copies of each histone H2A, H2B, H3, and H4. Nucleosomes are folded into higher-order structures that are stabilized by linker histones. Chromatin structure can be altered by enzymes that posttranslationally modify histones (e.g., through phosphorylation, acetylation, methylation, or ubiquitination) or by ATP-driven chromatin-remodeling complexes that alter nucleosome position and/or composition. 

Small tfbiquitin-like modifier represents a family of evolutionary conserved proteins that are distantly related in amino-acid sequence to ubiquitin, but share the same structural folding with ubiquitin proteins. SUMO proteins are covalently conjugated to protein substrates by an isopeptide bond through their carboxyl termini. SUMO addition to lysine residues of target proteins, termed SUMOylation, mediates post-transla-tional modification and requires a set of enzymes that are distinct from those that act on ubiquitin. SUMOylation regulates the activity of a variety of tar get proteins including transcription factors. 

Prior to this work, ubiquitin staining had been the most sensitive marker of Lewy body pathology. By doublelabeling, the number of a-synuclein-positive structures was greater than that stained for ubiquitin, suggesting that the ubiquitination of a-synuclein occurs after assembly. 

Glial cytoplasmic inclusions are strongly immunoreac-tive for a-synuclein and filaments isolated from the brains of patients with multiple system atrophy are labeled by a-synuclein antibodies [10]. As in dementia with Lewy bodies, assembled a-synuclein is nitrated and phosphory-lated at S129, and the number of a-synuclein-positive structures exceeds that stained by anti-ubiquitin antibodies, confirming that the accumulation of a-synuclein precedes ubiquitination. Filament morphologies and their staining characteristics were found to be similar to those of filaments extracted from the brains of patients with Parkinson s disease and dementia with Lewy bodies. 

Robust decreases in the expression of the various proteasome subunits and ubiquitin-conjugating enzymes have been described in prefrontal cortex in schizophrenia. Neuronal ubiquitin and proteasomes play an important role in the assembly, function and plasticity of the synapse. Structural proteins including tubulin and a-spectrin also show decreased expression in prefrontal cortex. 

The ubiquitin backbone structure has been determined using dipolar couplings as the sole source of structural restraints in the work reported by Hus et al. [105]. The resulting structure is practically identical to the NMR structure calculated from NOE and other... 

Two distinct structural elements play a role in the ubiquitination of a target protein (i) the E3 recognition site and (ii) the anchoring residue of the polyubiquitin chain. In most cases, it is believed, though it has been shown for only a few proteins, that the first ubiquitin moiety is transferred to an -NH2 group of an internal lysine residue in the substrate. The N-terminal domain of the target protein has attracted attention both as an E3 recognition domain and, recently, as a ubiquitination site. 

SoKOLiK, C. W. and Cohen, R. E. The structures of ubiquitin conjugates of yeast Iso-2-cytochrome c. J. Biol. 

---