German Center for Neurodegenerative Diseases - DZNE
The DZNE studies causes and mechanisms leading to the formation of neurodegenerative diseases. The aim is, by means of close collaboration between basic, health care and clinical researchers, to rapidly translate knowledge obtained in laboratories into therapeutic applications. Neurodegenerative diseases cannot be cured in most cases, but only treated palliatively. That is why the underlying pathomechanisms shall be elucidated using a variety of state-of-the art technologies at the DZNE. Of particular importance is structural biology as many factors that are important for neurodegeneration, such as mutation and post-translational modifications, alter the three-dimensional structure of proteins. It is therefore essential to characterize the three-dimensional structure of proteins in different pathological states. Proteins to be studied include intrinsically disordered proteins, proteins in membranes and protein complexes. Due to the dynamic nature and heterogeneity of many protein structures, NMR spectroscopy is particularly suited for structural biology studies in the area of neurodegeneration. NMR spectroscopy is a nanoscale microscopy technique monitoring biomolecular conformation on length scales down to 10-11 and time scales from nanoseconds to hours and longer. We further employ complementary methods such as mass spectrometry, electron microscopy and x-ray crystallography in our studies.
Publications:
Ukmar-Godec T, Fang P, Ibanez de Opakua A, Henneberg F, Godec A, Pan KT, Cima-Omori MS, Chari A, Mandelkow E, Urlaub H, Zweckstetter M; Proteasomal degradation of the intrinsically disordered protein tau at single-residue resolution. Sci Adv 2020, 6 (30), eaba3916. PubMed
Favretto F, Baker JD, Strohaker T, Andreas LB, Blair LJ, Becker S, Zweckstetter M; The Molecular Basis of the Interaction of Cyclophilin A with alpha-Synuclein. Angew Chem Int Ed Engl 2020, 59 (14), 5643-5646. PubMed
Ukmar-Godec T, Hutten S, Grieshop MP, Rezaei-Ghaleh N, Cima-Omori MS, Biernat J, Mandelkow E, Soding J, Dormann D, Zweckstetter M; Lysine/RNA-interactions drive and regulate biomolecular condensation. Nat Commun 2019, 10 (1), 2909. PubMed
Strohaker T, Jung BC, Liou SH, Fernandez CO, Riedel D, Becker S, Halliday GM, Bennati M, Kim WS, Lee SJ, Zweckstetter M, Structural heterogeneity of alpha-synuclein fibrils amplified from patient brain extracts. Nat Commun 2019, 10 (1), 5535. PubMed
Oroz J, Chang BJ, Wysoczanski P, Lee CT, Perez-Lara A, Chakraborty P, Hofele RV, Baker JD, Blair LJ, Biernat J, Urlaub H, Mandelkow E, Dickey CA, Zweckstetter M, Structure and pro-toxic mechanism of the human Hsp90/PPIase/Tau complex. Nat Commun 2018, 9 (1), 4532. PubMed
Boehning M, Dugast-Darzacq C, Rankovic M, Hansen AS, Yu T, Marie-Nelly H, McSwiggen DT, Kokic G, Dailey GM, Cramer P, Darzacq X, Zweckstetter M; RNA polymerase II clustering through carboxy-terminal domain phase separation. Nat Struct Mol Biol 2018, 25 (9), 833-840. PubMEd
Jaipuria G, Leonov A, Giller K, Vasa SK, Jaremko L, Jaremko M, Linser R, Becker S, Zweckstetter M, Cholesterol-mediated allosteric regulation of the mitochondrial translocator protein structure. Nat Commun 2017, 8, 14893. PubMed
Ambadipudi S, Biernat J, Riedel D, Mandelkow E, Zweckstetter M; Liquid-liquid phase separation of the microtubule-binding repeats of the Alzheimer-related protein Tau. Nat Commun 2017, 8 (1), 275. PubMed
Oroz J, Kim JH, Chang BJ, Zweckstetter M; Mechanistic basis for the recognition of a misfolded protein by the molecular chaperone Hsp90. Nat Struct Mol Biol 2017, 24 (4), 407-413. PubMed
Cabrales Fontela Y, Kadavath H, Biernat J, Riedel D, Mandelkow E, Zweckstetter M; Multivalent cross-linking of actin filaments and microtubules through the microtubule-associated protein Tau. Nat Commun 2017, 8 (1), 1981. PubMed
