Sequence-based determinants and prediction of fuzzy interactions in protein complexes.

By Márton Miskei, Attila Horváth, Michele Vendruscolo, Mónika Fuxreiter. 2020

96 citations recorded by the source corpus.

It is becoming increasingly recognized that intrinsically disordered proteins are involved in a wide variety of protein interaction modes. In addition to the well-known process of 'folding upon binding' (disorder-to-order transition), many examples of fuzzy complexes are emerging, when the interacting proteins remain to be disordered in the bound state (disorder-to-disorder transitions). Disordered regions may populate ordered and disordered states to different extents depending on the partner ('context-dependent binding'). Here we assemble three datasets comprising disorder-to-order, context-dependent and disorder-to-disorder transitions of 828 protein regions represented in 2157 complexes and elucidate the sequence-determinants of the different interaction modes. We found that fuzzy interactions originate in the lack the local sequence biases in a variety of proteins, which sample a wide range of structure and dynamics. Thus, we have developed the FuzPred method (http://protdyn-fuzpred.org) to predict the different binding modes of disordered proteins based on their amino acid sequence, without specifying their partners. We thus illustrate how the amino acid sequences of proteins can encode a wide range of conformational changes upon binding, including dynamical transitions from disordered to ordered and from disordered to disordered states, resulting in a variety of different interaction modes.

Subfields: Materials Chemistry, Molecular Biology

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In Materials Chemistry

1. Wing Yiu Choy
2. Carter J. Wilson
3. Mikko Karttunen

In Molecular Biology

1. Wing Yiu Choy
2. Carter J. Wilson
3. Mikko Karttunen

Citations in the corpus

• AlphaFold2 and its applications in the fields of biology and medicine (2023, neutral): “Although many approaches have been tried, 204 – 207 it is dif fi cult for existing methods to predict the morphology, dynamics and interactions of disordered regions of proteins in solutions.”
• AlphaFold2: A Role for Disordered Protein/Region Prediction? (2022, background): “, order-to-disorder, disorderto-order, disorder-to-disorder) that an IDP may undergo [62,69].”