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Institut de Biologie StructuraleGrenoble / France

Integrated NMR and cryo-EM atomic-resolution structure determination of a half-megadalton enzyme complex

Given their complexity, the structure determination of high molecular weight biological machinery often remains a challenge for experimental methods available to structuralists. Researchers from the MEM, NMR and DYNAMOP groups at IBS, in collaboration with the University of Frankfurt and the NIH, have developed an integrated structure determination approach that simultaneously uses NMR and EM data to overcome the limits of each of these methods. The approach enables structure determination of the 468 kDa large dodecameric aminopeptidase TET2 to a precision and accuracy below 1 Å. The resulting structure exceeds current standards of NMR and EM methods in terms of molecular weight and precision. Importantly, the approach is successful even in cases where only medium-resolution cryo-EM data are available and thus opens new perspectives for solving the structure of complex biological systems.

Integrated NMR and cryo-EM atomic-resolution structure determination of a half-megadalton enzyme complex. Gauto DF, Estrozi LF, Schwieters CD, Effantin G, Macek P, Sounier R, Sivertsen AC, Schmidt E, Kerfah R, Mas G, Colletier JP, Güntert P, Favier A, Schoehn G, Schanda P, Boisbouvier J. Nature Communications ;10(1):2697