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Biomacromolecules, such as proteins, often exhibit significant motions intimately associated with their function. Intrinsically disordered proteins and proteins with intrinsically disordered regions, although extremely important for a plethora of cellular functions, are difficult to structurally characterize at the atomic level because the experimental parameters report on ensemble and time averages. Here, we demonstrate for the C-terminal domain of the human immunodeficiency virus type 1 capsid protein that NMR and, in particular, residual dipolar couplings (RDCs) measured for the folded portion of the protein can inform on the structural preferences of the unstructured portion using RDC-prediction tools and the maximum occurrence approach.

Hypothesis Amorphous Magnesium-Calcium Phosphate (AMCP) particles in the distal small intestine have been shown to have a fundamental role in mammals’ immune-surveillance mechanisms. Their formation in the gut lumen and their stability against crystallization are expected to depend upon physiological conditions such as pH and [Mg2+]. Knowing the influence of these parameters on AMCP stability would allow to predict the presence and the activity of the particles in physiological or pathological conditions. Experiments We performed the synthesis of AMCP particles at physiological temperature, in phosphate buffer at variable pH from ∼7.0 to 7.4. The stability of the particles was then tested by dispersing them in different conditions of [Mg2+], pH and concentration, so to mimic different biological conditions. The particles were characterized in terms of morphology, crystallinity, chemical composition and porosity. Findings The characterization showed that we managed to prepare AMCPs with features matching those of the endogenous particles. Both the lifetime of the amorphous phase and the nature of the formed crystalline material were found to depend upon [Mg2+], pH and concentration. This article paves the way for the comprehension of possible dysfunctions of the gut immune-surveillance mechanisms due to imbalances of these physico-chemical parameters.