Robert A. Lamb
John Evans Professor
Viral glycoproteins, ion channels, and RNA-binding proteins
Our laboratory is investigating the molecular structure and the mechanism of replication of two enveloped RNA viruses: influenza virus and the paramyxovirus SV5. Both viruses cause diseases in humans and animals, with important biological and socioeconomic consequences.
The influenza viruses and the paramyxovirus SV5 encode seven integral membrane proteins: HA, NA, HN, F, M2, NB, and SH, that exhibit very different membrane topologies and range in size from 566 to 44 amino acids. We are particularly interested in the method of translocation of these proteins across the membrane of the endoplasmic reticulum, the role of glycosylation, and aspects of correct tertiary folding and oligomerization. These processes are a prerequisite for transport along the exocytic pathway; we are identifying cellular chaperone proteins that assist them. Analyzing the functions of these glycoproteins forms another area of interest. One project concerns the mechanism by which the F proteins cause viral-cell and cell-cell fusion. The second project entails the study of the HN glycoprotein, including its role in fusion, the signals and pathways regulating its internalization from the cell surface, and subsequent degradation. The M2 and NB proteins are critical in the replication cycle of influenza viruses. We used electrophysiological methods to demonstrate that the M2 protein has an ion-channel activity that is blocked by the antiviral drug amantadine. In collaboration with Professor Lawrence Pinto, we are performing a detailed structure-function analysis of this minimalistic ion channel. The potential ion-channel activity of NB is also under study.
Reversible Inhibition of Fusion Activity of a Paramyxovirus Fusion Protein by an Engineered Disulfide Bond in the Membrane-Proximal External Region. Zokarkar A, Connolly SA, Jardetzky TS, and Lamb RA. Journal of Virology. 2012 November;86(22):12397-12401.
Structure of the cleavage-activated prefusion form of the parainfluenza virus 5 fusion protein. Welch BD, Liu Y, Kors CA, Leser GP, Jardetzky TS, and Lamb RA. PNAS. 2012 October 9;109(41):16672-16677.
Filamentous Influenza Virus Enters Cells via Macropinocytosis. Rossman JS, Leser GP, Jardetzky TS, and Lamb RA. Journal of Virology. 2012 October;86(20):10950-10960.
Fusion activation by a headless parainfluenza virus 5 hemagglutinin-neuraminidase stalk suggests a modular mechanism for triggering. Bose S, Zokarkar A, Welch BD, Leser GP, Jardetzky TS, and Lamb RA. PNAS. 2012 September 25;109(39):E2625-E2634.
Structure of the Ulster Strain Newcastle Disease Virus Hemagglutinin-Neuraminidase Reveals Auto-Inhibitory Interactions Associated with Low Virulence. Yuan P, Paterson RG, Leser GP, Lamb RA, and Jardetzky TS. PLoS Pathogens. 2012 August 9;8(8):e1002855.
Structure of the human metapneumovirus fusion protein with neutralizing antibody identifies a pneumovirus antigenic site. Wen X, Krause JC, Leser GP, Cox RG, Lamb RA, Williams JV, Crowe JE, and Jardetzky TS. Nature Structural & Molecular Biology. 2012 April;19(4):461-463.
The Paramyxovirus Fusion Protein C-Terminal Region: Mutagenesis Indicates an Indivisible Protein Unit. Zokarkar A and Lamb RA. Journal of Virology. 2012 March;86(5):2600-2609.
Capture and imaging of a prehairpin fusion intermediate of the paramyxovirus PIV5. Kim YH, Donald JE, Grigoryan G, Leser GP, Fadeev AY, Lamb RA, and DeGrado WF. PNAS. 2011 December 27;108(52):20992-20997.
Comparison of differing cytopathic effects in human airway epithelium of parainfluenza virus 5 (W3A), parainfluenza virus type 3, and respiratory syncytial virus. Zhang L, Collins PL, Lamb RA, and Pickles RJ. Virology. 2011 December 5;421(1):67-77.
Structure and Mutagenesis of the Parainfluenza Virus 5 Hemagglutinin-Neuraminidase Stalk Domain Reveals a Four-Helix Bundle and the Role of the Stalk in Fusion Promotion. Bose S, Welch BD, Kors CA, Yuan P, Jardetzky TS, and Lamb RA. Journal of Virology. 2011 December;85(24):12855-12866.
Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk. Yuan P, Swanson KA, Leser GP, Paterson RG, Lamb RA, and Jardetzky TS. PNAS. 2011 September 6;108(36):14920-14925.
View all publications by Robert A. Lamb listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.