Arne Möller
Group Leader


Professor at Osnabrück University since 2020

Former member of

Department of Structural Biology
Max Planck Institute of Biophysics
Max-von-Laue-Str. 3

60438 Frankfurt am Main, Germany

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SORTEM - Characterisation of Sortilin-receptor complexes

Dr. Arne Möller, Research Group Leader, Department of Structural Biology,
Max Planck Institute of Biophysics

The proper interaction of individual neurons over synapses demands precise control of their formation. Neurotrophins (NTs) are secreted messengers that tightly bind to neuronal surface receptors and are involved in such control. Among the group of neurotrophic receptors are sortilins. Sortilin receptors are type-I membrane proteins that are mainly, but not exclusively, expressed in the brain and are involved in neurotrophic signaling. They play a crucial role in the modulation of synaptic plasticity and neuronal development and are functionally linked to neurodegenerative disorders such as Schizophrenia, Alzheimer’s and Huntington’s disease.

Currently, it is not understood if sortilins are capable of transducing signals on their own, however, it is well established that they engage in signaling complexes as co-receptors. Typically, they form a ternary complex together with the primary cellular receptor and its molecular messenger. The specific function of the sortilin receptor in these complexes can vary. In some cases they are essential for the complex while in others they function as modulators, which can dramatically increase the signaling of the primary receptor and also boost its affinity to the messenger.

My lab is especially interested to study how sortilin signaling complexes are formed and to understand the molecular mechanics that sortilins exert on the main receptor. We hypothesize that sortilins stabilize the primary receptor in a specific conformation that improves its interaction with the messenger and therefore increases affinity and signaling of the complex. To validate this hypothesis detailed structural knowledge is essential. The molecular weight of full-length sortilin receptor complexes, their extensive glycosylation, requirement of a hydrophobic environment and low amounts that can be isolated challenge protein crystallography and NMR for structure determination; therefore, our strategy is based on transmission electron microscopy (TEM).  


The family of sortilins consists of five members that all share the unique VPS10p domain. Additional domains characterize SorCS1-3 and SorLA. My preliminary data has revealed that SorCS1-3 can exist as dimers or monomers. 

Hidden twins: SorCS receptors form dimers.
Preliminary studies on purified hSorCS1 (a) and hSorCS2 (b) in negative stain revealed that the majority of individual particles are composed as dimers (while monomers are still present (see (a)). Superposition of reference-free 3D surfaces, revealed C2 symmetry of rigid dimers, as can also be seen in the superposition (c).




    Ye Q, Rosenberg SC, Moeller A, Speir JA, Su TY, Corbett KD (2015) TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching. Elife 4.


    Kang Y, Zhou XE, Gao X, He Y, Liu W, Ishchenko A, Barty A, White TA, Yefanov O, Han GW, et al. (2015) Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature 523, 561–567.


    Moeller A*, Lee SC*, Tao H, Speir JA, Chang G, Urbatsch IL, Potter CS, Carragher B, Zhang Q (2015) Distinct conformational spectrum of homologous multidrug ABC transporters. Structure 23, 450–460.


    Leung JH, Schurig-Briccio LA, Yamaguchi M, Moeller A, Speir JA, Gennis RB, Stout CD (2015) Division of labor in transhydrogenase by alternating proton translocation and hydride transfer. Science 347, 178–181.


    Bhabha G, Cheng H-C, Zhang N, Moeller A, Liao M, Speir JA, Cheng Y, Vale RD (2014) Allosteric communication in the dynein motor domain. Cell 159, 857–868.


    Tao H*, Lee SC*, Moeller A*, Roy RS, Siu FY, Zimmermann J, Stevens RC, Potter CS, Carragher B, Zhang Q (2013) Engineered nanostructured β-sheet peptides protect membrane proteins. Nat Methods 10, 759–761.


    Campbell MG, Cheng A, Brilot AF, Moeller A, Lyumkis D, Veesler D, Pan J, Harrison SC, Potter CS, Carragher B, et al. (2012). Movies of ice-embedded particles enhance resolution in electron cryo-microscopy. Structure 20, 1823–1828.


    Moeller A*, Kirchdoerfer RN*, Potter CS, Carragher B, Wilson IA (2012) Organization of the influenza virus replication machinery. Science 338, 1631–1634.


    Milazzo A-C, Cheng A, Moeller A, Lyumkis D, Jacovetty E, Polukas J, Ellisman MH, Xuong N-H, Carragher B, Potter CS (2011) Initial evaluation of a direct detection device detector for single particle cryo-electron microscopy. J Struct Biol 176, 404–408.

    * Co-first author