Harris D Bernstein Genetics and Biochemistry Branch of the National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Biography Publications Institution JoVE Articles Harris D Bernstein Harris Bernstein is a Senior Investigator in the Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive Diseases, National Institutes of Health (NIH) in Bethesda, Maryland. He received an undergraduate degree from Harvard University and a Ph.D. from MIT. Dr. Bernstein has a long-standing interest in understanding how proteins are translocated across or inserted into the membranes of both pathogenic and non-pathogenic bacteria.As a post-doctoral fellow in Peter Walter’s lab at the University of California at San Francisco he discovered a bacterial homolog of the signal recognition particle (SRP), an essential protein targeting factor that at the time was believed to exist only in mammalian cells. As an independent investigator at the NIH he continued to work on SRP and the Sec pathway in E. coli. He and his colleagues have also investigated the mechanism by which the expression of secA is regulated at the level of translation by ribosome stalling.His research group currently studies the assembly of bacterial outer membrane proteins and the secretion of virulence factors by a specialized pathway (the type V or “autotransporter” pathway) that is utilized by a wide variety of Gram-negative pathogens. Recently his group has also begun to investigate protein secretion in Bacteroides fragilis, a prominent member of the human gut microbiome. Publications Identification of a Novel Post-insertion Step in the Assembly of a Bacterial Outer Membrane Protein Molecular Microbiology. Aug, 2018 | Pubmed ID: 30107065 The Bam Complex Catalyzes Efficient Insertion of Bacterial Outer Membrane Proteins into Membrane Vesicles of Variable Lipid Composition The Journal of Biological Chemistry. Feb, 2018 | Pubmed ID: 29311257 Folding of a Bacterial Integral Outer Membrane Protein is Initiated in the Periplasm Nature Communications. 11, 2017 | Pubmed ID: 29101319 Selective Pressure for Rapid Membrane Integration Constrains the Sequence of Bacterial Outer Membrane Proteins Molecular Microbiology. Dec, 2017 | Pubmed ID: 28941249 Genomic Diversity of Enterotoxigenic Strains of Bacteroides Fragilis PloS One. Month, 2016 | Pubmed ID: 27348220 Enterohemorrhagic Reduce Mucus and Intermicrovillar Bridges in Human Stem Cell-derived Colonoids Cellular and Molecular Gastroenterology and Hepatology. Jan, 2016 | Pubmed ID: 26855967 Surface-Exposed Lipoproteins: An Emerging Secretion Phenomenon in Gram-Negative Bacteria Trends in Microbiology. Mar, 2016 | Pubmed ID: 26711681 An In Vitro Assay for Outer Membrane Protein Assembly by the BAM Complex Methods in Molecular Biology (Clifton, N.J.). Month, 2015 | Pubmed ID: 26427687 Looks Can Be Deceiving: Recent Insights into the Mechanism of Protein Secretion by the Autotransporter Pathway Molecular Microbiology. Jul, 2015 | Pubmed ID: 25881492 Analysis of the Outer Membrane Proteome and Secretome of Bacteroides Fragilis Reveals a Multiplicity of Secretion Mechanisms PloS One. Month, 2015 | Pubmed ID: 25658944 Of Linkers and Autochaperones: an Unambiguous Nomenclature to Identify Common and Uncommon Themes for Autotransporter Secretion Molecular Microbiology. Jan, 2015 | Pubmed ID: 25345653 Reconstitution of Bacterial Autotransporter Assembly Using Purified Components ELife. Sep, 2014 | Pubmed ID: 25182416 Stepwise Folding of an Autotransporter Passenger Domain is Not Essential for Its Secretion The Journal of Biological Chemistry. Dec, 2013 | Pubmed ID: 24165126 Charge-dependent Secretion of an Intrinsically Disordered Protein Via the Autotransporter Pathway Proceedings of the National Academy of Sciences of the United States of America. Nov, 2013 | Pubmed ID: 24145447 Mutations in the Escherichia Coli Ribosomal Protein L22 Selectively Suppress the Expression of a Secreted Bacterial Virulence Factor Journal of Bacteriology. Jul, 2013 | Pubmed ID: 23625843 Mechanistic Link Between β Barrel Assembly and the Initiation of Autotransporter Secretion Proceedings of the National Academy of Sciences of the United States of America. Mar, 2013 | Pubmed ID: 23431155 Cell Biology: All Clear for Ribosome Landing Nature. Dec, 2012 | Pubmed ID: 23235870 Molecular Basis for the Activation of a Catalytic Asparagine Residue in a Self-cleaving Bacterial Autotransporter Journal of Molecular Biology. Jan, 2012 | Pubmed ID: 22094314 Sequential and Spatially Restricted Interactions of Assembly Factors with an Autotransporter Beta Domain Proceedings of the National Academy of Sciences of the United States of America. Aug, 2011 | Pubmed ID: 21646511 Residues in a Conserved α-helical Segment Are Required for Cleavage but Not Secretion of an Escherichia Coli Serine Protease Autotransporter Passenger Domain Journal of Bacteriology. Aug, 2011 | Pubmed ID: 21642456 The Translational Regulatory Function of SecM Requires the Precise Timing of Membrane Targeting Molecular Microbiology. Jul, 2011 | Pubmed ID: 21635582 The Double Life of a Bacterial Lipoprotein Molecular Microbiology. Mar, 2011 | Pubmed ID: 21338414 Type V Secretion: the Autotransporter and Two-Partner Secretion Pathways EcoSal Plus. Sep, 2010 | Pubmed ID: 26443787 Secretion of a Bacterial Virulence Factor is Driven by the Folding of a C-terminal Segment Proceedings of the National Academy of Sciences of the United States of America. Oct, 2010 | Pubmed ID: 20876094 The Conformation of a Nascent Polypeptide Inside the Ribosome Tunnel Affects Protein Targeting and Protein Folding Molecular Microbiology. Oct, 2010 | Pubmed ID: 20804452 Molecular Basis for the Structural Stability of an Enclosed β-barrel Loop Journal of Molecular Biology. Sep, 2010 | Pubmed ID: 20655928 Sequential Translocation of an Escherchia Coli Two-partner Secretion Pathway Exoprotein Across the Inner and Outer Membranes Molecular Microbiology. Jan, 2010 | Pubmed ID: 19968793 Interaction of an Autotransporter Passenger Domain with BamA During Its Translocation Across the Bacterial Outer Membrane Proceedings of the National Academy of Sciences of the United States of America. Nov, 2009 | Pubmed ID: 19850876 The Plasticity of a Translation Arrest Motif Yields Insights into Nascent Polypeptide Recognition Inside the Ribosome Tunnel Molecular Cell. Apr, 2009 | Pubmed ID: 19394297 Identification of a Post-targeting Step Required for Efficient Cotranslational Translocation of Proteins Across the Escherichia Coli Inner Membrane The Journal of Biological Chemistry. Apr, 2009 | Pubmed ID: 19211555 Incorporation of a Polypeptide Segment into the Beta-domain Pore During the Assembly of a Bacterial Autotransporter Molecular Microbiology. Jan, 2008 | Pubmed ID: 18047580 Autotransporter Structure Reveals Intra-barrel Cleavage Followed by Conformational Changes Nature Structural & Molecular Biology. Dec, 2007 | Pubmed ID: 17994105 Are Bacterial 'autotransporters' Really Transporters? Trends in Microbiology. Oct, 2007 | Pubmed ID: 17935998 Protein Secretion in Gram-negative Bacteria Via the Autotransporter Pathway Annual Review of Microbiology. Month, 2007 | Pubmed ID: 17506669 Cleavage of a Bacterial Autotransporter by an Evolutionarily Convergent Autocatalytic Mechanism The EMBO Journal. Apr, 2007 | Pubmed ID: 17347646 Characterization of a Novel Two-partner Secretion System in Escherichia Coli O157:H7 Journal of Bacteriology. May, 2007 | Pubmed ID: 17322314 The Surprising Complexity of Signal Sequences Trends in Biochemical Sciences. Oct, 2006 | Pubmed ID: 16919958 Translation Arrest Requires Two-way Communication Between a Nascent Polypeptide and the Ribosome Molecular Cell. Jun, 2006 | Pubmed ID: 16762832 An Unusual Signal Peptide Extension Inhibits the Binding of Bacterial Presecretory Proteins to the Signal Recognition Particle, Trigger Factor, and the SecYEG Complex The Journal of Biological Chemistry. Apr, 2006 | Pubmed ID: 16455668 Efficient Secretion of a Folded Protein Domain by a Monomeric Bacterial Autotransporter Molecular Microbiology. Nov, 2005 | Pubmed ID: 16262782 An Unusual Signal Peptide Facilitates Late Steps in the Biogenesis of a Bacterial Autotransporter Proceedings of the National Academy of Sciences of the United States of America. Jan, 2005 | Pubmed ID: 15615856 Conserved Tertiary Base Pairing Ensures Proper RNA Folding and Efficient Assembly of the Signal Recognition Particle Alu Domain Nucleic Acids Research. Month, 2004 | Pubmed ID: 15383645 Basic Amino Acids in a Distinct Subset of Signal Peptides Promote Interaction with the Signal Recognition Particle The Journal of Biological Chemistry. Nov, 2003 | Pubmed ID: 12949068 Signal Recognition Particle (SRP)-mediated Targeting and Sec-dependent Translocation of an Extracellular Escherichia Coli Protein The Journal of Biological Chemistry. Feb, 2003 | Pubmed ID: 12466262 DnaK Promotes the Selective Export of Outer Membrane Protein Precursors in SecA-deficient Escherichia Coli The Journal of Biological Chemistry. Dec, 2002 | Pubmed ID: 12403776 Trigger Factor Retards Protein Export in Escherichia Coli The Journal of Biological Chemistry. Nov, 2002 | Pubmed ID: 12205085 Evidence for a Novel GTPase Priming Step in the SRP Protein Targeting Pathway The EMBO Journal. Dec, 2001 | Pubmed ID: 11726508 The Targeting Pathway of Escherichia Coli Presecretory and Integral Membrane Proteins is Specified by the Hydrophobicity of the Targeting Signal Proceedings of the National Academy of Sciences of the United States of America. Mar, 2001 | Pubmed ID: 11248102 Physiological Basis for Conservation of the Signal Recognition Particle Targeting Pathway in Escherichia Coli Journal of Bacteriology. Apr, 2001 | Pubmed ID: 11244056 The Biogenesis and Assembly of Bacterial Membrane Proteins Current Opinion in Microbiology. Apr, 2000 | Pubmed ID: 10744997 The Structure of Multiple Polypeptide Domains Determines the Signal Recognition Particle Targeting Requirement of Escherichia Coli Inner Membrane Proteins Journal of Bacteriology. Aug, 1999 | Pubmed ID: 10419954 Membrane Protein Biogenesis: the Exception Explains the Rules Proceedings of the National Academy of Sciences of the United States of America. Dec, 1998 | Pubmed ID: 9843931 Protein Targeting: Getting into the Groove Current Biology : CB. Oct, 1998 | Pubmed ID: 9778518 Monitoring the Assembly of a Secreted Bacterial Virulence Factor Using Site-specific Crosslinking Olga Pavlova1, Raffaele Ieva1, Harris D Bernstein1 1Genetics and Biochemistry Branch of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health JoVE 51217 Imunologia e Infecção
Monitoring the Assembly of a Secreted Bacterial Virulence Factor Using Site-specific Crosslinking Olga Pavlova1, Raffaele Ieva1, Harris D Bernstein1 1Genetics and Biochemistry Branch of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health JoVE 51217 Imunologia e Infecção