Publications

Please click here to see my Google Scholar profile for more detail and citation numbers.

(37) Cho, C., Jang, J., Kang, Y.,...,Kim SJ,...,Song, J. (2019). Structural basis of nucleosome assembly by the Abo1 AAA+ ATPase histone chaperone. Nat Commun 10, 5764

(36) Jang, S., Kang, C., Yang, H.-S., Jung, T., Hebert, H., Chung, K. Y.,Kim SJ,...,Song, J.-J. (2019). Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase. Genes & Development.

(35) A. Padavannil, P.Sarkar, Kim SJ, T.Cagatay, J.Jiou, C.A. Brautigam, D.R. Tomchick, A.Sali et al. (2019) Importin-9 wraps around the H2A-H2B core to act as nuclear importer and histone chaperone. ELife, vol. 8, 2019, doi:10.7554/elife.43630

(34) A Gaber, Kim SJ, RM Kaake, M Benčina, N Krogan, A Šali, M Pavšič et al. (2018) EpCAM homo-oligomerization is not the basis for its role in cell-cell adhersion. Scientific reports, 8(1): 13269

(33) T Yoshizawa*, R Ali*, J Jiou, HYJ Fung, KA Burke, Kim SJ, et al. (2018) Nuclear import receptor inhibits phase separation of FUS through binding to multiple sites. Cell, 173(3):693-705. e22

(32) Kim SJ*, Fernandez-Martinez J*, Nudelman I*, Shi Y*, et al. (2018) Integrative Structure and Functional Anatomy of the Nuclear Pore Complex. Nature, 555:475-482

(31) Yoon J, Kim SJ, An S, Leitner A, et al. (2018) Integrative Structural Investigation on the Architecture of Human Importin4_Histone H3/H4_Asf1a Complex and Its Histone H3 Tail Binding. Journal of Molecular Biology, 430(6):822-841

(30) Viswanath S*, Bonomi M*, Kim SJ, et al. (2017) The molecular architecture of the yeast spindle pole body core determined by Bayesian integrative modeling. Molecular Biology of the Cell, 28(23):3298-3314

(29) Upla P*, Kim SJ*, Sampathkumar P*, Dutta K*, et al. (2017) Molecular Architecture of the Major Membrane Ring Component of the Nuclear Pore Complex. Structure, 25(3):434-445

(28) Fernandez-Martinez J*, Kim SJ*, Shi Y*, Upla P*, et al. (2016) Structure and Function of the Nuclear Pore Complex Cytoplasmic mRNA Export Platform. Cell, 167:1215–1228;

(27) Timney B, Raveh B, Mironska R, Trivedi J, Kim SJ, et al. (2016) Simple rules for passive diffusion through the nuclear pore complex. Journal of Cell Biology 215:1; doi: 10.1083/jcb.201601004;

(26) LoPiccolo J*, Kim SJ*, Shi Y, Wu B, et al. (2015) Assembly and Molecular Architecture of the Phosphoinositide 3-Kinase p85α homodimer. Journal of Biological Chemistry290:30390-30405;

(25) Carter L*, Kim SJ*, Schneidman-Duhovny D*, Stoehr J*, et al. (2015) Prion protein - antibody complexes characterized by chromatography-coupled small angle X-ray scattering. Biophys J 109: 793-805;

(24) Kim SJ*, Fernandez-Martinez J*, Sampathkumar P*, Martel A, et al. (2014) Integrative structure-function mapping of the nucleoporin Nup133 suggests a conserved mechanism for membrane anchoring of the nuclear pore complex. Mol Cell Proteomics mcp.M114.040915;

(23) Shi Y*, Fernandez-Martinez J*, Tjioe E*, Pellarin R*, Kim SJ*, et al. (2014) Structural characterization by cross-linking reveals the detailed architecture of a coatomer-related heptameric module from the nuclear pore complex. Mol Cell Proteomics mcp.M114.041673;

(22) Algret R, Fernandez-Martinez J, Shi Y, Kim SJ, Pellarin R, et al. (2014) Molecular architecture and function of the SEA complex, a modulator of the TORC1 pathway. Mol Cell Proteomics mcp.M114.039388;

(21) Bonomi M, Pellarin R, Kim SJ, Russel D, Sundin BA, et al. (2014) Determining protein complex structures based on a Bayesian model of in vivo FRET data. Mol Cell Proteomics mcp.M114.040824;

(20) Pieper U, Webb BM, Dong GQ, Schneidman-Duhovny D, Fan H, Kim SJ, et al. (2014) ModBase, a database of annotated comparative protein structure models and associated resources. Nucleic Acids Res 42:D336-346;

(19) Spill YG, Kim SJ, Schneidman-Duhovny D, Russel D, Webb B, et al. (2014) SAXS Merge: an automated statistical method to merge SAXS profiles using Gaussian processes. Journal of Synchrotron Radiation 21: 203-208;

(18) Matsumura Y, Shinjo M, Kim SJ, Okishio N, Gruebele M, et al. (2013) Transient helical structure during PI3K and Fyn SH3 domain folding. J Phys Chem B 117: 4836-4843;

(17) Sampathkumar P, Kim SJ, Upla P, Rice WJ, et al. (2013) Structure, dynamics, evolution, and function of a major scaffold component in the nuclear pore complex. Structure21:560-571, highlighted as a cover story;

(16) Martinez-Avila O, Wu S, Kim SJ, Cheng Y, Khan F, et al. (2012) Self-assembly of filamentous amelogenin requires calcium and phosphate: from dimers via nanoribbons to fibrils. Biomacromolecules 13: 3494-3502;

(15) Schneidman-Duhovny D, Kim SJ, Sali A (2012) Integrative structural modeling with small angle X-ray scattering profiles. BMC Struct Biol 12: 17;

(14) Schneidman-Duhovny D, Rossi A, Avila-Sakar A, Kim SJ, Velazquez-Muriel J, et al. (2012) A method for integrative structure determination of protein-protein complexes. Bioinformatics 28: 3282-3289;

(13) Sampathkumar P, Kim SJ, Manglicmot D, Bain KT, et al. (2012) Atomic structure of the nuclear pore complex targeting domain of a Nup116 homologue from the yeast, Candida glabrata. Proteins 80: 2110-2116;

(12) Sampathkumar P, Gheyi T, Miller SA, Bain KT, Dickey M, Bonanno JB, Kim SJ, et al. (2011) Structure of the C-terminal domain of Saccharomyces cerevisiae Nup133, a component of the nuclear pore complex. Proteins 79: 1672-1677;

(11) Webb B, Lasker K, Schneidman-Duhovny D, Tjioe E, Phillips J, Kim SJ, et al. (2011) Modeling of proteins and their assemblies with the integrative modeling platform. Network Biology: Methods and Applications 781: 377-397;

(10) Sampathkumar P, Ozyurt SA, Do J, Bain KT, Dickey M, Rodgers L, Gheyi T, Sali A, Kim SJ, et al. (2010) Structures of the autoproteolytic domain from the Saccharomyces cerevisiae nuclear pore complex component, Nup145. Proteins 78: 1992-1998;

(9) Kim SJ, Matsumura Y, Dumont C, Kihara H, Gruebele M (2009) Slowing down downhill folding: a three-probe study. Biophys J 97: 295-302;

(8) Born B, Kim SJ, Ebbinghaus S, Gruebele M, Havenith M (2009) The terahertz dance of water with the proteins: the effect of protein flexibility on the dynamical hydration shell of ubiquitin. Faraday Discuss 141: 161-173; discussion 175-207;

(7) Kim SJ (2008) Studies of protein-protein and protein-water interactions by small angle X-ray scattering, terahertz spectroscopy, ASMOS, and computer simulation: University of Illinois at Urbana-Champaign, Ph.D. Thesis

(6) Kim SJ, Born B, Havenith M, Gruebele M (2008) Real-time detection of protein-water dynamics upon protein folding byterahertz absorption spectroscopy. Angew Chem Int Ed Engl 47: 6486-6489, highlighted as an inside cover story;

(5) Ebbinghaus S, Kim SJ, Heyden M, Yu X, Gruebele M, et al. (2008) Protein sequence- and pH-dependent hydration probed by terahertz spectroscopy. J Am Chem Soc 130: 2374-2375;

(4) Kim SJ, Dumont C, Gruebele M (2008) Simulation-based fitting of protein-protein interaction potentials to SAXS experiments. Biophys J 94: 4924-4931;

(3) Ebbinghaus S, Kim SJ, Heyden M, Yu X, Heugen U, et al. (2007) An extended dynamical hydration shell around proteins. Proc Natl Acad Sci USA 104: 20749-20752;

(2) Matsumura Y, Shinjo M, Kim SJ, Li J, Jin X, et al. (2007) Guanidine hydrochloride-induced unfolding transition of pseudo-WT Fyn SH3 at pH 6 in the presence of 45% ethylene glycol at 4 ºC. Photon Factory Activity Report 24:218

(1) Dumont C, Matsumura Y, Kim SJ, Li J, Kondrashkina E, et al. (2006) Solvent-tuning the collapse and helix formation time scales of lambda(6-85)*. Protein Sci 15: 2596-2604;

Publicaction Highlights

(32) Kim SJ*, Fernandez-Martinez J*, Nudelman I*, Shi Y*, et al. (2017) Structure and Functional Anatomy of the Nuclear Pore Complex. Nature, in press

- Despite the central role of Nuclear Pore Complexes (NPCs) as gatekeepers of RNA and protein transport between the cytoplasm and nucleoplasm, their large size and dynamic nature have impeded a full structural and functional elucidation. Here, we have determined a subnanometer precision structure for the entire 552-protein yeast NPC by satisfying diverse data, including primarily stoichiometry, a cryo-electron tomography map, and chemical cross-links. The structure reveals the NPC’s functional elements in unprecedented detail. The NPC is built of sturdy diagonal columns to which are attached connector cables, imbuing both strength and flexibility, and tying together all other elements of the NPC, including membrane-interacting regions and RNA processing platforms. Inwardly-directed anchors create a high density of transport factor-docking Phe-Gly repeats in the NPC’s central channel, organized in distinct functional units. Taken together, this integrative structure allows us to rationalize the architecture, transport mechanism, and evolutionary origins of the NPC.

(28) Fernandez-Martinez J*, Kim SJ*, Shi Y*, Upla P*, et al. (2016) Structure and Function of the Nuclear Pore Complex Cytoplasmic mRNA Export Platform. Cell, 167:1215–1228;

- The last steps in mRNA export and remodeling are performed by the Nup82 complex, a large conserved assembly at the cytoplasmic face of the nuclear pore complex (NPC). By integrating diverse structural data, I have determined the molecular architecture of the native Nup82 complex at subnanometer precision. The complex consists of two compositionally identical multiprotein subunits that adopt different configurations. The Nup82 complex fits into the NPC through the outer ring Nup84 complex. Our map shows that this entire 14-MDa Nup82-Nup84 complex assembly positions the cytoplasmic mRNA export factor docking sites and messenger ribonucleoprotein (mRNP) remodeling machinery right over the NPC’s central channel rather than on distal cytoplasmic filaments, as previously supposed. We suggest that this configuration efficiently captures and remodels exporting mRNP particles immediately upon reaching the cytoplasmic side of the NPC.

- Nup133 is an essential scaffold protein of the NPC’s outer ring structure. I developed an integrative modeling approach that produced atomic models for multiple states of Nup133, based on the X-ray crystal structures, 19 small angle X-ray scattering (SAXS) profiles, and 23 negative-stain electron microscopy (EM) class averages. The resulting multi-state structure model was validated with mutational studies and 45 chemical cross-links, allowing annotation of a potential ArfGAP1 lipid packing sensor (ALPS) motif in Nup133. The ALPS motifs are scattered throughout the NPC’s scaffold and play a major role in the assembly and membrane anchoring of the NPC in the nuclear envelope.

- The outer rings of the nuclear pore complex (NPC) are mainly formed by the Nup84 complex in budding yeast, composed of seven component proteins. By computationally integrating the 286 chemical cross-links (two complementary cross-linkers of DSS and EDC) together with other sources of information coming from electron microscopy, X-ray crystallography, and etc., I determined a detailed structure of the endogenous Nup84 complex. The unprecedented detail of the Nup84 complex provided information on the conformational flexibility of the assembly and an evolutionary relationship between vesicle coating complexes and the NPC.

- The TORC1 pathway controls eukaryotic cell growth and cellular responses to a variety of signals (e.g. nutrients, hormones, and stresses). The SEA complex is situated at the vacuole membrane in yeast and implicated in the cellular response to different stresses via its regulation of the TORC1 pathway. For the very first time, I determined the molecular architecture of the SEA complex, using computational methods based on an integrative modeling approach that combines an extensive dataset coming from affinity purification, chemical cross-linking, and etc. The resulting model revealed that the SEA complex emerges as a platform that can coordinate both structural and enzymatic activities necessary for the effective functioning of the TORC1 pathway.

- I and co-workers studied whether amelogenin, the main enamel matrix protein, could self-assemble into ribbon-like structures in physiologic solutions. Ribbons of 17 nm wide were observed to grow several micrometers in length, requiring calcium, phosphate, and pH 4.0-6.0. The pH range suggests that the formation of ion bridges through protonated histidine residues is essential to self-assembly, supported by a statistical analysis of 212 phosphate-binding proteins predicting 12 phosphate-binding histidines. Thermophoretic analysis verified the importance of calcium and phosphate in self-assembly. I performed the small angle X-ray scattering experiments characterizing amelogenin dimers with dimensions fitting the cross-section of the amelogenin ribbon, which led to the hypothesis that antiparallel dimmers are the building blocks of the ribbons. Over 5-7 days, ribbons self-organized into bundles composed of aligned ribbons mimicking the structure of enamel crystallites in enamel rods. These observations confirm reports of filamentous organic components in developing enamel and provide a new model for matrix-templated enamel mineralization.

(15) Schneidman-Duhovny D, Kim SJ, Sali A (2012) Integrative structural modeling with small angle X-ray scattering profiles. BMC Struct Biol 12: 17

- Recent technological advances enabled high-throughput collection of Small Angle X-ray Scattering (SAXS) profiles of biological macromolecules. Thus, computational methods for integrating SAXS profiles into structural modeling are needed more than ever. Here, we review specifically the use of SAXS profiles for the structural modeling of proteins, nucleic acids, and their complexes. First, the approaches for computing theoretical SAXS profiles from structures are presented. Second, computational methods for predicting protein structures, dynamics of proteins in solution, and assembly structures are covered. Third, we discuss the use of SAXS profiles in integrative structure modeling approaches that depend simultaneously on several data types.

(6) Kim SJ, Born B, Havenith M, Gruebele M (2008) Real-time detection of protein-water dynamics upon protein folding by terahertz absorption spectroscopy. Angew Chem Int Ed Engl 47: 6486-6489, highlighted as an inside cover story

- I developed Kinetic terahertz absorption (KITA) for the first time that uses a picosecond-duration terahertz pulse to monitor direct changes in solvent dynamics during the folding of ubiquitin on a reaction time scale of milliseconds to seconds, combined with small angle X-ray scattering (SAXS), fluorescence, and circular dichroism spectroscopy data. The KITA spectroscopy has provided insight into what happens in the period of time between these folded and unfolded states. Within less than 10 ms, the motion of the water network changed at the same time as the protein was restructured. These two processes took place practically simultaneously, strongly correlated. These observations supported the suggestion that water plays a fundamental role in protein folding, and thus in protein function, and does not stay passive.

(3) Ebbinghaus S, Kim SJ, Heyden M, Yu X, Heugen U, et al. (2007) An extended dynamical hydration shell around

proteins. Proc Natl Acad Sci USA 104: 20749-20752;

-The focus in protein folding has been very much on the protein backbone and sidechains. However, hydration waters make comparable contributions to the structure and energy of proteins. The coupling between fast hydration dynamics and protein dynamics is considered to play an important role in protein folding. Fundamental questions of protein hydration include, how far out into the solvent does the influence of the biomolecule reach, how is the water affected, and how are the properties of the hydration water influenced by the separation between protein molecules in solution? We showed that Terahertz spectroscopy directly probes such solvation dynamics around proteins, and determines the width of the dynamical hydration layer. We also investigated the dependence of solvation dynamics on protein concentration. We observed an unexpected nonmonotonic trend in the measured terahertz absorbance of the five helix bundle protein lambda* 6–85 as a function of the protein: water molar ratio. The trend can be explained by overlapping solvation layers around the proteins. Molecular dynamics simulations indicated water dynamics in the solvation layer around one protein to be distinct from bulk water out to ~10 Å. At higher protein concentrations such that solvation layers overlap, the calculated absorption spectrum varies non-monotonically, qualitatively consistent with the experimental observations. The experimental data suggested an influence on the correlated water network motion beyond 20 Å, greater than the pure structural correlation length usually observed.