TY - JOUR AB - Atomic-resolution structure determination is crucial for understanding protein function. Cryo-EM and NMR spectroscopy both provide structural information, but currently cryo-EM does not routinely give access to atomic-level structural data, and, generally, NMR structure determination is restricted to small (<30 kDa) proteins. We introduce 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 by combining secondary-structure information obtained from near-complete magic-angle-spinning NMR assignments of the 39 kDa-large subunits, distance restraints from backbone amides and ILV methyl groups, and a 4.1 Å resolution EM map. The resulting structure exceeds current standards of NMR and EM structure determination in terms of molecular weight and precision. Importantly, the approach is successful even in cases where only medium-resolution cryo-EM data are available. AU - Gauto, Diego F. AU - Estrozi, Leandro F. AU - Schwieters, Charles D. AU - Effantin, Gregory AU - Macek, Pavel AU - Sounier, Remy AU - Sivertsen, Astrid C. AU - Schmidt, Elena AU - Kerfah, Rime AU - Mas, Guillaume AU - Colletier, Jacques-Philippe AU - Güntert, Peter AU - Favier, Adrien AU - Schoehn, Guy AU - Schanda, Paul AU - Boisbouvier, Jerome ID - 8405 JF - Nature Communications KW - General Biochemistry KW - Genetics and Molecular Biology KW - General Physics and Astronomy KW - General Chemistry SN - 2041-1723 TI - Integrated NMR and cryo-EM atomic-resolution structure determination of a half-megadalton enzyme complex VL - 10 ER -