Young-Hwa Song's Publications List

The peroxisomal receptor Pex19p forms a helical mPTS recognition domain.

2010-08-22T15:05:20Z

The protein Pex19p functions as a receptor and chaperone of peroxisomal membrane proteins (PMPs). The crystal structure of the folded C-terminal part of the receptor reveals a globular domain that displays a bundle of three long helices in an antiparallel arrangement. Complementary functional experiments, using a range of truncated Pex19p constructs, show that the structured alpha-helical domain b...

Nicole Schueller, Simon J Holton, Krisztian Fodor, Morlin Milewski, Petr Konarev, Will A Stanley, Janina Wolf, Ralf Erdmann, Wolfgang Schliebs, Young-Hwa Song, Matthias Wilmanns (2010) EMBO J 29: 15 2491-2500

Stoichiometric protein complex formation and over-expression using the prokaryotic native operon structure.

2010-08-22T15:05:20Z

In prokaryotes, operon encoded proteins often form protein-protein complexes. Here, we show that the native structure of operons can be used to efficiently overexpress protein complexes. This study focuses on operons from mycobacteria and the use of Mycobacterium smegmatis as an expression host. We demonstrate robust and correct stoichiometric expression of dimers to higher oligomers. The expressi...

Christian Poulsen, Simon Holton, Arie Geerlof, Matthias Wilmanns, Young-Hwa Song (2010) FEBS Lett 584: 4 669-674

Proteome-wide identification of mycobacterial pupylation targets.

2010-08-22T15:05:20Z

Mycobacteria use a unique system for covalently modifying proteins based on the conjugation of a small protein, referred to as prokaryotic ubiquitin-like protein (PUP). In this study, we report a proteome-wide analysis of endogenous pupylation targets in the model organism Mycobacterium smegmatis. On affinity capture, a total of 243 candidate pupylation targets were identified by two complementary...

Christian Poulsen, Yusuf Akhter, Amy Hye-Won Jeon, Gerold Schmitt-Ulms, Helmut E Meyer, Anja Stefanski, Kai Stühler, Matthias Wilmanns, Young-Hwa Song (2010) Mol Syst Biol 6:

High-resolution structural analysis of mammalian profilin 2a complex formation with two physiological ligands: the formin homology 1 domain of mDia1 and the proline-rich domain of VASP.

2010-08-22T15:05:20Z

Profilins are small proteins capable of binding actin, poly-l-proline and other proline-rich sequences, and phosphatidylinositol (4,5)-bisphosphate. A number of proline-rich ligands for profilin have been characterised, including proteins of the Ena/VASP and formin families. We have determined the high-resolution crystal structures of mouse profilin 2a in complex with peptides from two functionall...

Petri Kursula, Inari Kursula, Marzia Massimi, Young-Hwa Song, Joshua Downer, Will A Stanley, Walter Witke, Matthias Wilmanns (2008) J Mol Biol 375: 1 270-290

Bimolecular fluorescence complementation in structural biology.

2010-08-22T15:05:20Z

Bimolecular fluorescence complementation is a method of probing protein-ligand interactions under physiological conditions. It provides a state-of-the-art tool to examine interactions observed in 3D structures of multi-component protein complexes, either to validate new experimental structures or to assess the correctness of homology models. Applications of the method range from homo- and hetero-o...

Young-Hwa Song, Matthias Wilmanns (2008) Methods 45: 3 219-222

Palindromic assembly of the giant muscle protein titin in the sarcomeric Z-disk.

2010-08-22T15:05:20Z

The Z-disk of striated and cardiac muscle sarcomeres is one of the most densely packed cellular structures in eukaryotic cells. It provides the architectural framework for assembling and anchoring the largest known muscle filament systems by an extensive network of protein-protein interactions, requiring an extraordinary level of mechanical stability. Here we show, using X-ray crystallography, how...

Peijian Zou, Nikos Pinotsis, Stephan Lange, Young-Hwa Song, Alexander Popov, Irene Mavridis, Olga M Mayans, Mathias Gautel, Matthias Wilmanns (2006) Nature 439: 7073 229-233

Nucleotide-induced conformations in the neck region of dimeric kinesin.

2010-08-22T15:09:39Z

The neck region of kinesin constitutes a key component in the enzyme's walking mechanism. Here we applied cryoelectron microscopy and image reconstruction to investigate the location of the kinesin neck in dimeric and monomeric constructs complexed to microtubules. To this end we enhanced the visibility of this region by engineering an SH3 domain into the transition between neck linker and neck co...

Georgios Skiniotis, Thomas Surrey, Stephan Altmann, Heinz Gross, Young-Hwa Song, Eckhard Mandelkow, Andreas Hoenger (2003) EMBO J 22: 7 1518-1528

Single-molecule investigation of the interference between kinesin, tau and MAP2c.

2010-08-22T15:09:39Z

Motor proteins and microtubule-associated proteins (MAPs) play important roles in cellular transport, regulation of shape and polarity of cells. While motor proteins generate motility, MAPs are thought to stabilize the microtubule tracks. However, the proteins also interfere with each other, such that MAPs are able to inhibit transport of vesicles and organelles in cells. In order to investigate t...

Arne Seitz, Hiroaki Kojima, Kazuhiro Oiwa, Eva-Maria Mandelkow, Young-Hwa Song, Eckhard Mandelkow (2002) EMBO J 21: 18 4896-4905

Structure of a fast kinesin: implications for ATPase mechanism and interactions with microtubules.

2010-08-22T15:09:39Z

We determined the crystal structure of the motor domain of the fast fungal kinesin from Neurospora crassa (NcKin). The structure has several unique features. (i) Loop 11 in the switch 2 region is ordered and enables one to describe the complete nucleotide-binding pocket, including three inter-switch salt bridges between switch 1 and 2. (ii) Loop 9 in the switch 1 region bends outwards, making the ...

Y H Song, A Marx, J Müller, G Woehlke, M Schliwa, A Krebs, A Hoenger, E Mandelkow (2001) EMBO J 20: 22 6213-6225

Dynamics and cooperativity of microtubule decoration by the motor protein kinesin.

2010-08-22T15:09:39Z

We describe a theoretical and experimental analysis of the interaction between microtubules and dimeric motor proteins (kinesin, NCD), with special emphasis on the stoichiometry of the interaction, cooperative effects, and their consequences for the interpretation of biochemical and image reconstruction results. Monomeric motors can bind equivalently to microtubules without interference, at a stoi...

A Vilfan, E Frey, F Schwabl, M Thormählen, Y H Song, E Mandelkow (2001) J Mol Biol 312: 5 1011-1026

Surface topography of microtubule walls decorated with monomeric and dimeric kinesin constructs.

2010-08-22T15:09:39Z

The surface topography of opened-up microtubule walls (sheets) decorated with monomeric and dimeric kinesin motor domains was investigated by freeze-drying and unidirectional metal shadowing. Electron microscopy of surface-shadowed specimens produces images with a high signal/noise ratio, which enable a direct observation of surface features below 2 nm detail. Here we investigate the inner and out...

A Hoenger, M Doerhoefer, G Woehlke, P Tittmann, H Gross, Y H Song, E Mandelkow (2000) Biol Chem 381: 9-10 1001-1011

The structure of the nucleotide-binding site of kinesin.

2010-08-22T15:09:39Z

Kinesin is a microtubule-based motor protein responsible for anterograde transport of vesicles and organelles in nerve axons and other cell types. The energy necessary for this transport is derived from the hydrolysis of ATP which is thought to induce conformational changes in the protein. We have solved the X-ray crystal structures of rat brain kinesin in three conditions intended to mimic differ...

J Müller, A Marx, S Sack, Y H Song, E Mandelkow (1999) Biol Chem 380: 7-8 981-992

Interaction of monomeric and dimeric kinesin with microtubules.

2010-08-22T15:09:39Z

The binding stoichiometry of kinesin to microtubules was determined using several biochemical and biophysical approaches (chemical crosslinking, binding assays, scanning transmission electron microscopy (STEM), image reconstruction, and X-ray scattering). The results show that each tubulin dimer associates with one kinesin head, irrespective of whether kinesin occurs in a monomeric or dimeric form...

M Thormählen, A Marx, S A Müller, Y Song, E M Mandelkow, U Aebi, E Mandelkow (1998) J Mol Biol 275: 5 795-809

On the structure of microtubules, tau, and paired helical filaments.

2010-08-22T15:09:39Z

Microtubules and their associated proteins form the basis of axonal transport; they are degraded during the neuronal degeneration in Alzheimer's disease. This article surveys recent results on the structure of microtubules, tau protein, and PHFs. Microtubules have been investigated by electron microscopy and image processing after labeling them with the head domain of the motor protein kinesin. Th...

E Mandelkow, Y H Song, O Schweers, A Marx, E M Mandelkow (1995) Neurobiol Aging 16: 3 347-354

The microtubule lattice--dynamic instability of concepts.

2010-08-22T15:09:39Z

In the February 1995 issue of trends in CELL BIOLOGY, Linda Amos presented her view of our current understanding of the lattice structure of microtubules, 20 years after publication of the original paper describing the A- and B-lattices for flagellar microtubules. However, the question of the lattices of flagellar and cytoplasmic microtubules remains a matter for debate. In this article, Eckhard M...

E Mandelkow, Y H Song, E M Mandelkow (1995) Trends Cell Biol 5: 7 262-266

The anatomy of flagellar microtubules: polarity, seam, junctions, and lattice.

2010-08-22T15:09:39Z

Although the overall structures of flagellar and cytoplasmic microtubules are understood, many details have remained a matter of debate. In particular, studies of the arrangement of tubulin subunits have been hampered by the low contrast of the tubulin subunits. This problem can now be addressed by the kinesin decoration technique. We have shown previously that the recombinant kinesin head domain ...

Y H Song, E Mandelkow (1995) J Cell Biol 128: 1-2 81-94