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Intrinsic Disorder (intrinsic + disorder)
Selected AbstractsProtein tandem repeats , the more perfect, the less structuredFEBS JOURNAL, Issue 12 2010Julien Jorda We analysed the structural properties of protein regions containing arrays of perfect and nearly perfect tandem repeats. Naturally occurring proteins with perfect repeats are practically absent among the proteins with known 3D structures. The great majority of such regions in the Protein Data Bank are found in the proteins designed de novo. The abundance of natural structured proteins with tandem repeats is inversely correlated with the repeat perfection: the chance of finding natural structured proteins in the Protein Data Bank increases with a decrease in the level of repeat perfection. Prediction of intrinsic disorder within the tandem repeats in the SwissProt proteins supports the conclusion that the level of repeat perfection correlates with their tendency to be unstructured. This correlation is valid across the various species and subcellular localizations, although the level of disordered tandem repeats varies significantly between these datasets. On average, in prokaryotes, tandem repeats of cytoplasmic proteins were predicted to be the most structured, whereas in eukaryotes, the most structured portion of the repeats was found in the membrane proteins. Our study supports the hypothesis that, in general, the repeat perfection is a sign of recent evolutionary events rather than of exceptional structural and (or) functional importance of the repeat residues. [source] Abundance of intrinsic disorder in SV-IV, a multifunctional androgen-dependent protein secreted from rat seminal vesicleFEBS JOURNAL, Issue 4 2008Silvia Vilasi The potent immunomodulatory, anti-inflammatory and procoagulant properties of protein no. 4 secreted from the rat seminal vesicle epithelium (SV-IV) have previously been found to be modulated by a supramolecular monomer,trimer equilibrium. More structural details that integrate experimental data into a predictive framework have recently been reported. Unfortunately, homology modelling and fold-recognition strategies were not successful in creating a theoretical model of the structural organization of SV-IV. It was inferred that the global structure of SV-IV is not similar to that of any protein of known three-dimensional structure. Reversing the classical approach to the sequence,structure,function paradigm, in this paper we report novel information obtained by comparing the physicochemical parameters of SV-IV with two datasets composed of intrinsically unfolded and ideally globular proteins. In addition, we analyse the SV-IV sequence by several publicly available disorder-oriented predictors. Overall, disorder predictions and a re-examination of existing experimental data strongly suggest that SV-IV needs large plasticity to efficiently interact with the different targets that characterize its multifaceted biological function, and should therefore be better classified as an intrinsically disordered protein. [source] Genetic Hypercalciuric Stone-Forming Rats Have a Primary Decrease in BMD and Strength,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2009Marc Grynpas Abstract Kidney stone patients often have a decrease in BMD. It is unclear if reduced BMD is caused by a primary disorder of bone or dietary factors. To study the independent effects of hypercalciuria on bone, we used genetic hypercalciuric stone-forming (GHS) rats. GHS and control (Ctl) rats were fed a low Ca (0.02% Ca, LCD) or a high Ca (1.2% Ca, HCD) diet for 6 wk in metabolic cages. All comparisons are to Ctl rats. Urine Ca was greater in the GHS rats on both diets. GHS fed HCD had reduced cortical (humerus) and trabecular (L1,L5 vertebrae) BMD, whereas GHS rats fed LCD had a reduction in BMD similar to Ctl. GHS rats fed HCD had a decrease in trabecular volume and thickness, whereas LCD led to a ,20-fold increase in both osteoid surface and volume. GHS rats fed HCD had no change in vertebral strength (failure stress), ductibility (failure strain), stiffness (modulus), or toughness, whereas in the humerus, there was reduced ductibility and toughness and an increase in modulus, indicating that the defect in mechanical properties is mainly manifested in cortical, rather than trabecular, bone. GHS rat cortical bone is more mineralized than trabecular bone and LCD led to a decrease in the mineralization profile. Thus, the GHS rats, fed an ample Ca diet, have reduced BMD with reduced trabecular volume, mineralized volume, and thickness, and their bones are more brittle and fracture prone, indicating that GHS rats have an intrinsic disorder of bone that is not secondary to diet. [source] The solution structure of ZNF593 from Homo sapiens reveals a zinc finger in a predominately unstructured proteinPROTEIN SCIENCE, Issue 3 2008Paulette L. Hayes Abstract Here, we report the solution structure of ZNF593, a protein identified in a functional study as a negative modulator of the DNA-binding activity of the Oct-2 transcription factor. ZNF593 contains a classic C2H2 zinc finger domain flanked by about 40 disordered residues on each terminus. Although the protein contains a high degree of intrinsic disorder, the structure of the zinc finger domain was resolved by NMR spectroscopy without a need for N- or C-terminal truncations. The tertiary structure of the zinc finger domain is composed of a ,-hairpin that positions the cysteine side chains for zinc coordination, followed by an atypical kinked ,-helix containing the two histidine side chain ligands. The structural topology of ZNF593 is similar to a fragment of the double-stranded RNA-binding protein Zfa and the C-terminal zinc finger of MBP-1, a human enhancer binding protein. The structure presented here will provide a guide for future functional studies of how ZNF593 negatively modulates the DNA-binding activity of Oct-2, a POU domain-containing transcription factor. Our work illustrates the unique capacity of NMR spectroscopy for structural analysis of folded domains in a predominantly disordered protein. [source] | ||||||||||