TY - JOUR
T1 - Extreme disorder in an ultrahigh-affinity protein complex
AU - Borgia, Alessandro
AU - Borgia, Madeleine B.
AU - Bugge, Katrine
AU - Kissling, Vera M.
AU - Heidarsson, Pétur O.
AU - Fernandes, Catarina B.
AU - Sottini, Andrea
AU - Soranno, Andrea
AU - Buholzer, Karin J.
AU - Nettels, Daniel
AU - Kragelund, Birthe B.
AU - Best, Robert B.
AU - Schuler, Benjamin
N1 - Publisher Copyright:
© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Molecular communication in biology is mediated by protein interactions. According to the current paradigm, the specificity and affinity required for these interactions are encoded in the precise complementarity of binding interfaces. Even proteins that are disordered under physiological conditions or that contain large unstructured regions commonly interact with well-structured binding sites on other biomolecules. Here we demonstrate the existence of an unexpected interaction mechanism: the two intrinsically disordered human proteins histone H1 and its nuclear chaperone prothymosin-α associate in a complex with picomolar affinity, but fully retain their structural disorder, long-range flexibility and highly dynamic character. On the basis of closely integrated experiments and molecular simulations, we show that the interaction can be explained by the large opposite net charge of the two proteins, without requiring defined binding sites or interactions between specific individual residues. Proteome-wide sequence analysis suggests that this interaction mechanism may be abundant in eukaryotes.
AB - Molecular communication in biology is mediated by protein interactions. According to the current paradigm, the specificity and affinity required for these interactions are encoded in the precise complementarity of binding interfaces. Even proteins that are disordered under physiological conditions or that contain large unstructured regions commonly interact with well-structured binding sites on other biomolecules. Here we demonstrate the existence of an unexpected interaction mechanism: the two intrinsically disordered human proteins histone H1 and its nuclear chaperone prothymosin-α associate in a complex with picomolar affinity, but fully retain their structural disorder, long-range flexibility and highly dynamic character. On the basis of closely integrated experiments and molecular simulations, we show that the interaction can be explained by the large opposite net charge of the two proteins, without requiring defined binding sites or interactions between specific individual residues. Proteome-wide sequence analysis suggests that this interaction mechanism may be abundant in eukaryotes.
UR - http://www.scopus.com/inward/record.url?scp=85042739773&partnerID=8YFLogxK
U2 - 10.1038/nature25762
DO - 10.1038/nature25762
M3 - Article
C2 - 29466338
AN - SCOPUS:85042739773
SN - 0028-0836
VL - 555
SP - 61
EP - 66
JO - Nature
JF - Nature
IS - 7694
ER -