Structural disorder is an essential ingredient for function in many proteins and protein complexes. Fuzzy complexes describe the many instances where disorder is maintained as a critical element of protein interactions. In this minireview we discuss how intramolecular fuzzy interactions function in signaling complexes. Focussing on the Src family of kinases, we argue that the intrinsically disordered domains that are unique for each of the family members and display a clear fingerprint of long range interactions in Src, might have critical roles as functional sensor or effectors and mediate allosteric communication via fuzzy interactions.
The function of the intrinsically disordered Unique domain of the Src family of tyrosine kinases (SFK), where the largest differences between family members are concentrated, remains poorly understood. Recent studies in c-Src have demonstrated that the Unique region forms transient interactions, described as an intramolecular fuzzy complex, with the SH3 domain and suggested that similar complexes could be formed by other SFKs. Src and Lyn are members of a distinct subfamily of SFKs. Lyn is a key player in the immunologic response and exists in two isoforms originating from alternative splicing in the Unique domain. We have used NMR to compare the intramolecular interactions in the two isoforms and found that the alternatively spliced segment interacts specifically with the so-called RT-loop in the SH3 domain and that this interaction is abolished when a polyproline ligand binds to the SH3 domain. These results support the generality of the fuzzy complex formation in distinct subfamilies of SFKs and its physiological role, as the naturally occurring alternative splicing modulates the interactions in this complex.
HVAC systems are composed of different noise sources and paths. The non-attenuated propagation of noise through the system has detrimental effects on acoustic comfort of people inside the premises. To mitigate the propagated noise, parallel baffle splitters are used which reduce the
transmitted noise through acoustic coatings. Different methods have been developed to predict the insertion loss of those elements, however, if the input data is not well known these models can lead to deviated results. On the other hand, the use of splitter in HVAC systems produces pressure
drop which can damage the equipment used if that is not well predicted. Different models are available in the literature, which relates dimensional features and design velocity to estimate the pressure drop coefficient. However, models can give overestimated results. In this work an experimental
rig was implemented to assess a splitter installed inside of a test duct. Measurements were performed to estimate insertion loss and pressure drop coefficient, following the guidelines exposed on the ISO 7235 standard. The results were compared with analytic methods. Finally, a numerical method
analysis of the test rig was performed, showing the correlation between these results and the experimental data.
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