Abundance of intrinsic disorder in SV-IV, a multifunctional androgen-dependent protein secreted from rat seminal vesicle

Abstract

The potent immunomodulatory, anti-inflammatory and procoagulant properties of the protein no. 4 secreted from the rat seminal vesicle epithelium (SV-IV) have been previously 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 any protein of known three-dimensional structure. Reversing the classical approach to the sequence-structure-function paradigm, in this paper we report on novel information obtained by comparing physicochemical parameters of SV-IV with two datasets made of intrinsically unfolded and ideally globular proteins. In addition, we have analysed 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 be therefore better classified as an intrinsically disordered protein.

Tick receptor for outer surface protein A from Ixodes ricinus — the first intrinsically disordered protein involved in vector-microbe recognition

“…Studies conducted over the last decade showed that approximately one-third of all eukaryotic proteins contain disordered regions 6 . IDPs perform various functions due to their ability to recognize and selectively bind multiple partners 7 8 9 . TROSPA from ticks belonging to Ixodidae has been reported to interact with at least two pathogen-derived effectors 2 3 4 .…”