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Ralf Langen, PhD

Professor of Physiology & Neuroscience

Director, Protein Structure Center, Zilkha Neurogenetic Institute

Director of the Ph.D. Program in Medical Physiology, Co-Director, Ph.D. Program in Medical Biophysics

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Phone +1 323 442 1323
Email langen@usc.edu
CTSI Profile

Publications

  • Pleiotropic effects of mutant huntingtin on retinopathy in two mouse models of Huntington’s disease Neurobiol Dis. 2025 Feb; 205:106780. . View in PubMed
  • TDP43 and huntingtin Exon-1 undergo a conformationally specific interaction that strongly alters the fibril formation of both proteins J Biol Chem. 2024 Sep; 300(9):107660. . View in PubMed
  • Retraction Note: Pericyte degeneration causes white matter dysfunction in the mouse central nervous system Nat Med. 2024 Apr; 30(4):1215. . View in PubMed
  • Fluorescent protein tagging promotes phase separation and alters the aggregation pathway of huntingtin exon-1 J Biol Chem. 2024 01; 300(1):105585. . View in PubMed
  • Molecular basis of Q-length selectivity for the MW1 antibody-huntingtin interaction J Biol Chem. 2023 04; 299(4):104616. . View in PubMed
  • The Dynamic Interactions of a Multitargeting Domain in Ameloblastin Protein with Amelogenin and Membrane Int J Mol Sci. 2023 Feb 09; 24(4). . View in PubMed
  • Lysine acetylation regulates the interaction between proteins and membranes Nat Commun. 2021 11 09; 12(1):6466. . View in PubMed
  • Amplification of neurotoxic HTTex1 assemblies in human neurons Neurobiol Dis. 2021 11; 159:105517. . View in PubMed
  • Huntingtin fibrils with different toxicity, structure, and seeding potential can be interconverted Nat Commun. 2021 07 13; 12(1):4272. . View in PubMed
  • An Amphipathic Alpha-Helix Domain from Poliovirus 2C Protein Tubulate Lipid Vesicles Viruses. 2020 12 18; 12(12). . View in PubMed
  • Structural Model of the Proline-Rich Domain of Huntingtin Exon-1 Fibrils Biophys J. 2020 11 17; 119(10):2019-2028. . View in PubMed
  • Discovery of Small Molecule Inhibitors of Huntingtin Exon 1 Aggregation by FRET-Based High-Throughput Screening in Living Cells ACS Chem Neurosci. 2020 08 05; 11(15):2286-2295. . View in PubMed
  • Annexin B12 Trimer Formation is Governed by a Network of Protein-Protein and Protein-Lipid Interactions Sci Rep. 2020 03 24; 10(1):5301. . View in PubMed
  • Structure of Membrane-Bound Huntingtin Exon 1 Reveals Membrane Interaction and Aggregation MechanismsStructure. 2019 10 01; 27(10):1570-1580. e4. . View in PubMed
  • The Mitochondrial Peptide Humanin Targets but Does Not Denature Amyloid Oligomers in Type II Diabetes J Am Chem Soc. 2019 09 11; 141(36):14168-14179. . View in PubMed
  • Lipid-modulation of membrane insertion and refolding of the apoptotic inhibitor Bcl-xL Biochim Biophys Acta Proteins Proteom. 2019 Jul – Aug; 1867(7-8):691-700. . View in PubMed
  • E46K-like a-synuclein mutants increase lipid interactions and disrupt membrane selectivity J Biol Chem. 2019 06 21; 294(25):9799-9812. . View in PubMed
  • The folding equilibrium of huntingtin exon 1 monomer depends on its polyglutamine tract J Biol Chem. 2018 12 21; 293(51):19613-19623. . View in PubMed
  • Directed Supramolecular Organization of N-BAR Proteins through Regulation of H0 Membrane Immersion Depth Sci Rep. 2018 11 06; 8(1):16383. . View in PubMed
  • Membranes as modulators of amyloid protein misfolding and target of toxicity Biochim Biophys Acta Biomembr. 2018 Sep; 1860(9):1863-1875. . View in PubMed
  • Heterotetrameric annexin A2/S100A10 (A2t) is essential for oncogenic human papillomavirus trafficking and capsid disassembly, and protects virions from lysosomal degradation Sci Rep. 2018 08 03; 8(1):11642. . View in PubMed
  • Identification of distinct conformations associated with monomers and fibril assemblies of mutant huntingtin Hum Mol Genet. 2018 07 01; 27(13):2330-2343. . View in PubMed
  • Pericyte degeneration causes white matter dysfunction in the mouse central nervous system Nat Med. 2018 03; 24(3):326-337. . View in PubMed
  • The 17-residue-long N terminus in huntingtin controls stepwise aggregation in solution and on membranes via different mechanisms J Biol Chem. 2018 02 16; 293(7):2597-2605. . View in PubMed
  • The Mitochondrial-Derived Peptides, HumaninS14G and Small Humanin-like Peptide 2, Exhibit Chaperone-like Activity Sci Rep. 2017 08 10; 7(1):7802. . View in PubMed
  • Membrane remodeling by amyloidogenic and non-amyloidogenic proteins studied by EPR J Magn Reson. 2017 07; 280:127-139. . View in PubMed
  • Structural insights into the activation mechanism of dynamin-like EHD ATPases Proc Natl Acad Sci U S A. 2017 05 30; 114(22):5629-5634. . View in PubMed
  • Identification and Structural Characterization of the N-terminal Amyloid Core of Orb2 isoform A Sci Rep. 2016 12 06; 6:38265. . View in PubMed
  • Hydration Dynamics of a Peripheral Membrane Protein J Am Chem Soc. 2016 09 14; 138(36):11526-35. . View in PubMed
  • Diabetic Risk Factors Promote Islet Amyloid Polypeptide Misfolding by a Common, Membrane-mediated Mechanism Sci Rep. 2016 08 17; 6:31094. . View in PubMed
  • a-Synuclein Amyloid Fibrils with Two Entwined, Asymmetrically Associated Protofibrils J Biol Chem. 2016 Jan 29; 291(5):2310-8. . View in PubMed
  • O-GlcNAc modification blocks the aggregation and toxicity of the protein a-synuclein associated with Parkinson’s disease Nat Chem. 2015 Nov; 7(11):913-20. . View in PubMed
  • Membrane Curvature-sensing and Curvature-inducing Activity of Islet Amyloid Polypeptide and Its Implications for Membrane Disruption J Biol Chem. 2015 Oct 23; 290(43):25782-93. . View in PubMed
  • Structural Mechanisms of Mutant Huntingtin Aggregation Suppression by the Synthetic Chaperonin-like CCT5 Complex Explained by Cryoelectron Tomography J Biol Chem. 2015 Jul 10; 290(28):17451-61. . View in PubMed
  • Solid-State Nuclear Magnetic Resonance on the Static and Dynamic Domains of Huntingtin Exon-1 Fibrils Biochemistry. 2015 Jun 30; 54(25):3942-9. . View in PubMed
  • Tubulation by amphiphysin requires concentration-dependent switching from wedging to scaffolding Structure. 2015 May 05; 23(5):873-881. . View in PubMed
  • Computer Modeling of Spin Labels: NASNOX, PRONOX, and ALLNOX Methods Enzymol. 2015; 563:569-93. . View in PubMed
  • Structural Characterization of Membrane-Curving Proteins: Site-Directed Spin Labeling, EPR, and Computational Refinement Methods Enzymol. 2015; 564:259-88. . View in PubMed
  • Nonaggregated a-synuclein influences SNARE-dependent vesicle docking via membrane binding Biochemistry. 2014 Jun 24; 53(24):3889-96. . View in PubMed
  • Endophilin A1 induces different membrane shapes using a conformational switch that is regulated by phosphorylation Proc Natl Acad Sci U S A. 2014 May 13; 111(19):6982-7. . View in PubMed
  • Structural insights into membrane interaction and caveolar targeting of dynamin-like EHD2 Structure. 2014 Mar 04; 22(3):409-420. . View in PubMed
  • Polyglutamine- and temperature-dependent conformational rigidity in mutant huntingtin revealed by immunoassays and circular dichroism spectroscopy PLoS One. 2014; 9(12):e112262. . View in PubMed
  • Hydration dynamics as an intrinsic ruler for refining protein structure at lipid membrane interfaces Proc Natl Acad Sci U S A. 2013 Oct 15; 110(42):16838-43. . View in PubMed
  • a-Synuclein oligomers with broken helical conformation form lipoprotein nanoparticles J Biol Chem. 2013 Jun 14; 288(24):17620-30. . View in PubMed
  • Visual arrestin interaction with clathrin adaptor AP-2 regulates photoreceptor survival in the vertebrate retina Proc Natl Acad Sci U S A. 2013 Jun 04; 110(23):9463-8. . View in PubMed
  • ß-Cell failure in type 2 diabetes: a case of asking too much of too few? Diabetes. 2013 Feb; 62(2):327-35.. View in PubMed
  • Rational design of potent domain antibody inhibitors of amyloid fibril assembly Proc Natl Acad Sci U S A. 2012 Dec 04; 109(49):19965-70. . View in PubMed
  • Idealized models of protofilaments of human islet amyloid polypeptide J Chem Inf Model. 2012 Nov 26; 52(11):2983-91. . View in PubMed
  • Membrane binding and self-association of the epsin N-terminal homology domain J Mol Biol. 2012 Nov 09; 423(5):800-17. . View in PubMed
  • Structural features and domain organization of huntingtin fibrils J Biol Chem. 2012 Sep 14; 287(38):31739-46. . View in PubMed
  • Remodeling of lipid vesicles into cylindrical micelles by a-synuclein in an extended a-helical conformation J Biol Chem. 2012 Aug 24; 287(35):29301-11. . View in PubMed
  • Diurnal, localized exposure of phosphatidylserine by rod outer segment tips in wild-type but not Itgb5-/- or Mfge8-/- mouse retina Proc Natl Acad Sci U S A. 2012 May 22; 109(21):8145-8. . View in PubMed
  • Semisynthetic, site-specific ubiquitin modification of a-synuclein reveals differential effects on aggregation J Am Chem Soc. 2012 Mar 28; 134(12):5468-71. . View in PubMed
  • Fibril structure of human islet amyloid polypeptide J Biol Chem. 2012 Feb 17; 287(8):5235-41. . View in PubMed
  • Secondary and tertiary structure of bacteriorhodopsin in the SDS denatured state Biochemistry. 2012 Feb 14; 51(6):1051-60. . View in PubMed
  • Computer modeling of nitroxide spin labels on proteins Biopolymers. 2012 Jan; 97(1):35-44. . View in PubMed
  • The S100A10 subunit of the annexin A2 heterotetramer facilitates L2-mediated human papillomavirus infection PLoS One. 2012; 7(8):e43519. . View in PubMed
  • Membrane curvature sensing by amphipathic helices: a single liposome study using a-synuclein and annexin B12 J Biol Chem. 2011 Dec 09; 286(49):42603-42614. . View in PubMed
  • Intracellular curvature-generating proteins in cell-to-cell fusion Biochem J. 2011 Dec 01; 440(2):185-93. . View in PubMed
  • A compact beta model of huntingtin toxicity J Biol Chem. 2011 Mar 11; 286(10):8188-8196. . View in PubMed
  • Beta-cell selective K(ATP)-channel activation protects beta-cells and human islets from human islet amyloid polypeptide induced toxicity Regul Pept. 2010 Dec 10; 165(2-3):158-62. . View in PubMed
  • Quantifying Membrane Curvature Generation of Drosophila Amphiphysin N-BAR Domains J Phys Chem Lett. 2010 Nov 16; 1(23):3401-3406. . View in PubMed
  • Membrane curvature induction and tubulation are common features of synucleins and apolipoproteins J Biol Chem. 2010 Oct 15; 285(42):32486-93. . View in PubMed
  • The effect of curcumin on human islet amyloid polypeptide misfolding and toxicity Amyloid. 2010 Sep; 17(3-4):118-28. . View in PubMed
  • Monitoring apoptosis and neuronal degeneration by real-time detection of phosphatidylserine externalization using a polarity-sensitive indicator of viability and apoptosis Nat Protoc. 2010 Aug; 5(8):1396-405. . View in PubMed
  • Multiple modes of endophilin-mediated conversion of lipid vesicles into coated tubes: implications for synaptic endocytosis J Biol Chem. 2010 Jul 23; 285(30):23351-8. . View in PubMed
  • A combinatorial NMR and EPR approach for evaluating the structural ensemble of partially folded proteins J Am Chem Soc. 2010 Jun 30; 132(25):8657-68. . View in PubMed
  • Roles of amphipathic helices and the bin/amphiphysin/rvs (BAR) domain of endophilin in membrane curvature generation J Biol Chem. 2010 Jun 25; 285(26):20164-70. . View in PubMed
  • Stacked sets of parallel, in-register beta-strands of beta2-microglobulin in amyloid fibrils revealed by site-directed spin labeling and chemical labeling J Biol Chem. 2010 May 28; 285(22):17137-47. . View in PubMed
  • Soluble and mature amyloid fibrils in drusen deposits Invest Ophthalmol Vis Sci. 2010 Mar; 51(3):1304-10. . View in PubMed
  • Fibrillar oligomers nucleate the oligomerization of monomeric amyloid beta but do not seed fibril formation J Biol Chem. 2010 Feb 26; 285(9):6071-9. . View in PubMed
  • Engineering a polarity-sensitive biosensor for time-lapse imaging of apoptotic processes and degeneration Nat Methods. 2010 Jan; 7(1):67-73. . View in PubMed
  • Annexin A5 directly interacts with amyloidogenic proteins and reduces their toxicity Biochemistry. 2009 Nov 10; 48(44):10568-76. . View in PubMed
  • Structure of membrane-bound alpha-synuclein from site-directed spin labeling and computational refinement Proc Natl Acad Sci U S A. 2008 Dec 16; 105(50):19666-71. . View in PubMed
  • Formation of soluble amyloid oligomers and amyloid fibrils by the multifunctional protein vitronectin Mol Neurodegener. 2008 Oct 21; 3:16. . View in PubMed
  • Fibrils with parallel in-register structure constitute a major class of amyloid fibrils: molecular insights from electron paramagnetic resonance spectroscopy Q Rev Biophys. 2008 Aug-Nov; 41(3-4):265-97. . View in PubMed
  • Structure of alpha-helical membrane-bound human islet amyloid polypeptide and its implications for membrane-mediated misfolding J Biol Chem. 2008 Jun 20; 283(25):17205-10. . View in PubMed
  • Investigation of alpha-synuclein fibril structure by site-directed spin labeling J Biol Chem. 2007 Aug 24; 282(34):24970-9. . View in PubMed
  • Membrane interaction of islet amyloid polypeptide Biochim Biophys Acta. 2007 Aug; 1768(8):2002-9. . View in PubMed
  • Structure and analysis of FCHo2 F-BAR domain: a dimerizing and membrane recruitment module that effects membrane curvature Structure. 2007 Jul; 15(7):839-52. . View in PubMed
  • Annexin B12 is a sensor of membrane curvature and undergoes major curvature-dependent structural changes J Biol Chem. 2007 Mar 30; 282(13):9996-10004. . View in PubMed
  • Side chain-dependent stacking modulates tau filament structure J Biol Chem. 2006 Dec 08; 281(49):37820-7. . View in PubMed
  • Inhibition of human IAPP fibril formation does not prevent beta-cell death: evidence for distinct actions of oligomers and fibrils of human IAPP Am J Physiol Endocrinol Metab. 2006 Dec; 291(6):E1317-24. . View in PubMed
  • Mechanism of endophilin N-BAR domain-mediated membrane curvature EMBO J. 2006 Jun 21; 25(12):2898-910. . View in PubMed
  • Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers J Clin Invest. 2006 Feb; 116(2):378-85. . View in PubMed
  • A novel calcium-independent peripheral membrane-bound form of annexin B12 Biochemistry. 2006 Jan 24; 45(3):934-42. . View in PubMed
  • Spin labeling analysis of amyloids and other protein aggregates Methods Enzymol. 2006; 413:122-39. . View in PubMed
  • Calcium- and membrane-induced changes in the structure and dynamics of three helical hairpins in annexin B12 Biochemistry. 2005 Dec 20; 44(50):16435-44. . View in PubMed
  • Light causes phosphorylation of nonactivated visual pigments in intact mouse rod photoreceptor cells J Biol Chem. 2005 Dec 16; 280(50):41184-91. . View in PubMed
  • A helical hairpin region of soluble annexin B12 refolds and forms a continuous transmembrane helix at mildly acidic pH J Biol Chem. 2005 Sep 16; 280(37):32398-404. . View in PubMed
  • Lipid membranes modulate the structure of islet amyloid polypeptide Biochemistry. 2005 Sep 13; 44(36):12113-9. . View in PubMed
  • Evidence for a triplex DNA conformation at the bcl-2 major breakpoint region of the t(14;18) translocation J Biol Chem. 2005 Jun 17; 280(24):22749-60. . View in PubMed
  • The conserved core domains of annexins A1, A2, A5, and B12 can be divided into two groups with different Ca2+-dependent membrane-binding properties Biochemistry. 2005 Mar 01; 44(8):2833-44. . View in PubMed
  • Alpha-synuclein structures from fluorescence energy-transfer kinetics: implications for the role of the protein in Parkinson’s disease Proc Natl Acad Sci U S A. 2004 Nov 23; 101(47):16466-71. . View in PubMed
  • Identifying structural features of fibrillar islet amyloid polypeptide using site-directed spin labeling J Biol Chem. 2004 Nov 12; 279(46):48420-5. . View in PubMed
  • Stability and strand asymmetry in the non-B DNA structure at the bcl-2 major breakpoint region J Biol Chem. 2004 Oct 29; 279(44):46213-25. . View in PubMed
  • Structure and dynamics of a helical hairpin that mediates calcium-dependent membrane binding of annexin B12 J Biol Chem. 2004 Jul 30; 279(31):32492-8. . View in PubMed
  • Template-assisted filament growth by parallel stacking of tau Proc Natl Acad Sci U S A. 2004 Jul 13; 101(28):10278-83. . View in PubMed
  • Structure of membrane-bound alpha-synuclein studied by site-directed spin labeling Proc Natl Acad Sci U S A. 2004 Jun 01; 101(22):8331-6. . View in PubMed
  • Structural organization of alpha-synuclein fibrils studied by site-directed spin labeling J Biol Chem. 2003 Sep 26; 278(39):37530-5. . View in PubMed
  • Global structural changes in annexin 12The roles of phospholipid, Ca2+, and pH. J Biol Chem. 2003 Aug 08; 278(32):30227-34. . View in PubMed
  • The Habc domain and the SNARE core complex are connected by a highly flexible linker Biochemistry. 2003 Apr 15; 42(14):4009-14. . View in PubMed
  • Structural and dynamic features of Alzheimer’s Abeta peptide in amyloid fibrils studied by site-directed spin labeling J Biol Chem. 2002 Oct 25; 277(43):40810-5. . View in PubMed
  • Rapid and selective binding to the synaptic SNARE complex suggests a modulatory role of complexins in neuroexocytosis J Biol Chem. 2002 Mar 08; 277(10):7838-48. . View in PubMed
  • Structure and dynamics of a helical hairpin and loop region in annexin 12: a site-directed spin labeling study Biochemistry. 2002 Feb 05; 41(5):1464-73. . View in PubMed
  • Calcium-dependent binding of annexin 12 to phospholipid bilayers: stoichiometry and implications Biochemistry. 2001 Jun 19; 40(24):7054-60. . View in PubMed
  • Homo- and heterooligomeric SNARE complexes studied by site-directed spin labeling J Biol Chem. 2001 Apr 20; 276(16):13169-77. . View in PubMed
  • Crystal structures of spin labeled T4 lysozyme mutants: implications for the interpretation of EPR spectra in terms of structure Biochemistry. 2000 Jul 25; 39(29):8396-405. . View in PubMed
  • Annexins V and XII insert into bilayers at mildly acidic pH and form ion channels Biochemistry. 2000 Mar 21; 39(11):3015-22. . View in PubMed
  • Structural features of the C-terminal domain of bovine rhodopsin: a site-directed spin-labeling study Biochemistry. 1999 Jun 22; 38(25):7918-24. . View in PubMed
  • A transmembrane form of annexin XII detected by site-directed spin labeling Proc Natl Acad Sci U S A. 1998 Nov 24; 95(24):14060-5. . View in PubMed
  • Recent advances in site-directed spin labeling of proteins Curr Opin Struct Biol. 1998 Oct; 8(5):649-56. . View in PubMed
  • Membrane-mediated assembly of annexins studied by site-directed spin labeling J Biol Chem. 1998 Aug 28; 273(35):22453-7. . View in PubMed
  • Structure and function in rhodopsin: topology of the C-terminal polypeptide chain in relation to the cytoplasmic loops Proc Natl Acad Sci U S A. 1997 Dec 23; 94(26):14267-72. . View in PubMed
  • Electrostatic control of GTP and GDP binding in the oncoprotein p21ras Structure. 1996 Apr 15; 4(4):475-89. . View in PubMed
  • Electron tunneling in proteins: role of the intervening medium Journal of Biological Inorganic Chemistry. 1996; 1(3):221. . View in PubMed
  • Electron tunneling in proteins: coupling through a beta strand Science. 1995 Jun 23; 268(5218):1733-5. . View in PubMed
  • Electron transfer in ruthenium-modified proteins J Bioenerg Biomembr. 1995 Jun; 27(3):295-302. . View in PubMed
  • Why have mutagenesis studies not located the general base in ras p21 Nat Struct Biol. 1994 Jul; 1(7):476-84. . View in PubMed
  • Protein control of iron-sulfur cluster redox potentials J Biol Chem. 1992 Dec 25; 267(36):25625-7. . View in PubMed
  • On the mechanism of guanosine triphosphate hydrolysis in ras p21 proteins Biochemistry. 1992 Sep 22; 31(37):8691-6. . View in PubMed
  • Effect of the Asn52—-Ile mutation on the redox potential of yeast cytochrome cTheory and experiment. J Mol Biol. 1992 Apr 05; 224(3):589-600. . View in PubMed

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