TY - JOUR
T1 - Sequence-Based Prediction of Fuzzy Protein Interactions
AU - Miskei, Marton
AU - Horvath, Attila
AU - Vendruscolo, Michele
AU - Fuxreiter, Monika
N1 - Publisher Copyright:
© 2020 The Author(s)
PY - 2020/3/27
Y1 - 2020/3/27
N2 - It is becoming increasingly recognised that disordered proteins may be fuzzy, in that they can exhibit a wide variety of binding modes. In addition to the well-known process of folding upon binding (disorder-to-order transition), many examples are emerging of interacting proteins that remain disordered in their bound states (disorder-to-disorder transitions). Furthermore, disordered proteins may populate ordered and disordered states to different extents depending on their partners (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 from local sequence compositions that promote the sampling of a wide range of different structures. Based on this observation, we developed the FuzPred method (http://protdyn-fuzpred.org) of predicting the binding modes of disordered proteins based on their amino acid sequences, 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 transitions from disordered to ordered and from disordered to disordered states.
AB - It is becoming increasingly recognised that disordered proteins may be fuzzy, in that they can exhibit a wide variety of binding modes. In addition to the well-known process of folding upon binding (disorder-to-order transition), many examples are emerging of interacting proteins that remain disordered in their bound states (disorder-to-disorder transitions). Furthermore, disordered proteins may populate ordered and disordered states to different extents depending on their partners (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 from local sequence compositions that promote the sampling of a wide range of different structures. Based on this observation, we developed the FuzPred method (http://protdyn-fuzpred.org) of predicting the binding modes of disordered proteins based on their amino acid sequences, 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 transitions from disordered to ordered and from disordered to disordered states.
KW - disordered proteins
KW - folding upon binding
KW - fuzzy complexes
KW - fuzzy interactions
KW - protein binding
UR - http://www.scopus.com/inward/record.url?scp=85081971258&partnerID=8YFLogxK
U2 - 10.1016/j.jmb.2020.02.017
DO - 10.1016/j.jmb.2020.02.017
M3 - Article
SN - 0022-2836
VL - 432
SP - 2289
EP - 2303
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 7
ER -