Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Transient exposure of a buried phosphorylation site in an autoinhibited protein Autoinhibition is a mechanism used to regulate protein function, often by making functional sites inaccessible through the interaction with a cis-acting inhibitory domain. Such autoinhibitory domains often display a substantial degree of structural disorder when unbound, and only become structured in the inhibited state. This conformational dynamics makes it difficult to study the structural origin of regulation, including effects of regulatory post-translational modifications. Here, we study the autoinhibition of the Dbl Homology domain in the protein Vav1 by the so-called acidic inhibitory domain. We use molecular simulations to study the process by which a mostly unstructured inhibitory domain folds upon binding and how transient exposure of a key buried tyrosine residue makes it accessible for phosphorylation. We show that the inhibitory domain, which forms a helix in the bound and inhibited stated, samples helical structures already before binding and that binding occurs via a molten-globule-like intermediate state. Together, our results shed light on key interactions that enable the inhibitory domain to sample a finely-tuned equilibrium between an inhibited and a kinase-accessible state.
4
The categories of this paper are: neuroscience
0
The categories of this paper are: genetics
29
The categories of this paper are: education
9
The categories of this paper are: synthetic
11
The categories of this paper are: cognition
17
The categories of this paper are: molecular
15
The categories of this paper are: developmental
20
The categories of this paper are: pharmacology
28
The categories of this paper are: communication
30
The categories of this paper are: scientific
27
The categories of this paper are: pathology
21
The categories of this paper are: toxicology
25
The categories of this paper are: bioengineering
10
The categories of this paper are: and
6
The categories of this paper are: plant
26
The categories of this paper are: biochemistry