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TY - JOUR AU - Borgia, Madeleine B. AU - Borgia, Alessandro AU - Best, Robert B. AU - Steward, Annette AU - Nettels, Daniel AU - Wunderlich, Bengt AU - Schuler, Benjamin AU - Clarke, Jane PY - 2011 DA - 2011/06/01 TI - Single-molecule fluorescence reveals sequence-specific misfolding in multidomain proteins JO - Nature SP - 662 EP - 665 VL - 474 IS - 7353 AB - Three in four human proteins have multiple domains, and the tendency of these proteins to aggregate increases with amino-acid sequence similarity. Single-molecule biophysics experiments now show that the misfolding is caused by strand-swapping between adjacent domains, and that diversification of sequence between neighbouring domains lowers the probability of misfolding. The work also indicates that such misfolding events are under kinetic rather than thermodynamic control. Because domain-swapped protein species have been implicated in various misfolding diseases, prevention of inter-domain misfolding may be protective against aggregation disorders. SN - 1476-4687 UR - https://doi.org/10.1038/nature10099 DO - 10.1038/nature10099 ID - Borgia2011 ER -