Hyung Ho Lee
Seoul National University · Biochemistry, Genetics and Molecular Biology
About the Lab
Professor Hyung Ho Lee's research lab specializes in structural biology and molecular mechanisms underlying critical cellular processes, with a focus on protein complexes involved in membrane dynamics, organelle biogenesis, and metabolic regulation. The lab employs X-ray crystallography and biochemical approaches to elucidate the architecture and function of multi-protein assemblies such as ESCRT machinery, BLOC-1, and the glycine cleavage system. Key research directions include understanding the structural basis of protein-protein and protein-DNA interactions in disease-relevant pathways, including cytokinesis, ribosome biogenesis, and one-carbon metabolism. The lab also investigates enzyme mechanisms and drug targeting in bacterial and human metabolic systems, particularly in the context of antimicrobial development and inherited metabolic disorders.
Research Overview
Research Output Trend
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Selected Papers
15The ESCRT (endosomal sorting complex required for transport) machinery is required for the scission of membrane necks in processes including the budding of HIV-1 and cytokinesis. An essential step in cytokinesis is recruitment of the ESCRT-I complex and the ESCRT-associated protein ALIX to the midbody (the structure that tethers two daughter cells) by the protein CEP55. Biochemical experiments show that peptides from ALIX and the ESCRT-I subunit TSG101 compete for binding to the ESCRT and ALIX-b
Human nucleophosmin (NPM; also known as B23, NO38, or numatrin), encoded by the NPM1 gene, is an abundant phosphoprotein in nucleoli.1-3 It is primarily localized to nucleolus but has been shown to shuttle between the cytoplasm and nucleus.4 Two isoforms of NPM, designated B23.1 and B23.2,5 consist of 294 and 259 amino acid residues, respectively, with B23.1 being the prevalent form in all tissues.5, 6 The C-terminal 35 amino acids of B23.1 are missing from B23.2 and the N-terminal 257 residues
BLOC-1 (biogenesis of lysosome-related organelles complex-1) is critical for melanosome biogenesis and has also been implicated in neurological function and disease. We show that BLOC-1 is an elongated complex that contains one copy each of the eight subunits pallidin, Cappuccino, dysbindin, Snapin, Muted, BLOS1, BLOS2, and BLOS3. The complex appears as a linear chain of eight globular domains, ∼300 Å long and ∼30 Å in diameter. The individual domains are flexibly connected such that the linear
The glycine cleavage system catalyzes the oxidative decarboxylation of glycine in bacteria and in mitochondria of animals and plants. Its deficiency in human causes nonketotic hyperglycinemia, an inborn error of glycine metabolism. T-protein, one of the four components of the glycine cleavage system,is a tetrahydrofolate dependent aminomethyltransferase. It catalyzes the transfer of the methylene carbon unit to tetrahydrofolate from the methylamine group covalently attached to the lipoamide arm
Enoyl-ACP reductase (ENR; EC 1.3.1.9), encoded by the fabI gene, is a key enzyme of the Type II fatty-acid biosynthetic system in prokaryotes and plants. It uses NADH or NADPH as the cofactor to reduce the double bond between C2 and C3 positions of a fatty acyl chain bound to the acyl carrier protein in the terminal rate-limiting step of the fatty acid chain elongation cycle.1 Because it shows low overall sequence homology with mammalian enzymes, it is a potential target for antibacterial discov
Although both the p53 and forkhead box (FOX) family proteins are key transcription factors associated with cancer progression, their direct relationship is unknown. Here, we found that FOX family proteins bind to the non-canonical homotypic cluster of the p53 promoter region (TP53). Analysis of crystal structures of FOX proteins (FOXL2 and FOXA1) bound to the p53 homotypic cluster indicated that they interact with a 2:1 stoichiometry accommodated by FOX-induced DNA allostery. In particular, FOX
FtsZ, a tubulin homologue, is an essential protein of the Z-ring assembly in bacterial cell division. It consists of two domains, the N-terminal and C-terminal core domains, and has a conserved C-terminal tail region. Lateral interactions between FtsZ protofilaments and several Z-ring associated proteins (Zaps) are necessary for modulating Z-ring formation. ZapD, one of the positive regulators of Z-ring assembly, directly binds to the C-terminal tail of FtsZ and promotes stable Z-ring formation
Bacterial phosphopantetheine adenylyltransferase (PPAT) catalyzes the penultimate step in the coenzyme A (CoA) biosynthetic pathway. It catalyzes the reversible transfer of an adenylyl group from ATP to 4'-phosphopantetheine (Ppant) to form dephospho-CoA (dPCoA) and pyrophosphate. Previous structural studies have revealed how several ligands are recognized by bacterial PPATs. ATP, ADP, Ppant and dPCoA bind to the same binding site in a highly similar manner, while CoA binds to a partially overla
IS200 transposases, present in many bacteria and Archaea, appear to be distinct from other groups of transposases. To provide a structural basis for understanding the action of IS200 transposases, we have determined the crystal structure of the SSO1474 protein from Sulfolobus solfataricus, a member of the IS200 family, in both Mn(2+)-bound and Mn(2+)-free forms. Its monomer fold is distinct from other classes of structurally characterized transposases. Two monomers form a tight dimer by exchangi
A novel Tc1-like transposable element has been identified as a new DNA transposon in the mud loach, Misgurnus mizolepis. The M. mizolepis Tc1-like transposon (MMTS) is comprised of inverted terminal repeats and a single gene that codes Tc1-like transposase. The deduced amino acid sequence of the transposase-encoding region of MMTS transposon contains motifs including DDE motif, which was previously recognized in other Tc1-like transposons. However, putative MMTS transposase has only 34-37% ident
The lysosomal membrane protein Niemann-Pick type C1 (NPC1) and Niemann-Pick type C2 (NPC2) are main players of cholesterol control in the lysosome and it is known that the mutation on these proteins leads to the cholesterol trafficking-related neurodegenerative disease, which is called the NPC disease. The mutation R518W or R518Q on the NPC1 is one of the type of disease-related mutation that causes cholesterol transports to be cut in half, which results in the accumulation of cholesterol and li
Research Areas
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