Dr. Amir Khan
Associate Professor, Biochemistry
Biography
Publications and Further Research Outputs
Peer-Reviewed Publications
Fram B, Su Y, Truebridge I, Riesselman A.J, Ingraham J.B, Passera A, Napier E, Thadani N.N, Lim S, Roberts K, Kaur G, Stiffler M.A, Marks D.S, Bahl C.D, Khan A.R, Sander C, Gauthier N.P, Simultaneous enhancement of multiple functional properties using evolution-informed protein design, Nature Communications, 15, (1), 2024
Strofaldi A, Khan A.R, McManus J.J, Surface Exposed Free Cysteine Suppresses Crystallization of Human γD-Crystallin, Journal of Molecular Biology, 433, (22), 2021
Benarroch Y, Juttukonda L, Sabharwal V, Boateng J, Khan A.R, Yarrington C, Wachman E.M, Taglauer E, Differential Expression of Rab5 and Rab7 Small GTPase Proteins in Placental Tissues From Pregnancies Affected by Maternal Coronavirus Disease 2019, Clinical Therapeutics, 43, (2), 2021, p308 - 318
Dieter Waschbuesch, Kerryn Berndsen, Pawel Lis, Axel Knebel, Yuko PY Lam, Dario R Alessi & Amir R Khan, Structural basis for the specificity of PPM1H phosphatase for Rab GTPases, EMBO reports, 22: e52675, 2021, p10.15252/embr.202152675
Dieter Waschbuesch, Elena Purlyte, Amir R Khan, Dual arginine recognition of LRRK2 phosphorylated Rab GTPases, Biophysical Journal, 120, (9), 2021, p1846 - 1855
Dieter Waschbusch, Elena Purlyte, Prosenjit Pal, Emma McGrath, Dario R. Alessi, Amir R. Khan, Structural Basis for Rab8a Recruitment of RILPL2 via LRRK2 Phosphorylation of Switch 2, Structure, 28, (1-12), 2020, p10.1016/j.str.2020.01.005
Dieter Waschbuesch and Amir R Khan, Phosphorylation of Rab GTPases in the regulation of membrane trafficking, Traffic, 21, (11), 2020, p712 - 719
Kearney A.M, Khan A.R, Crystal structure of the Rab-binding domain of Rab11 family-interacting protein 2, Acta Crystallographica Section F: Structural Biology Communications, 76, 2020, p357 - 363
Khan A.R, James S, Quinn M.K, Altan I, Charbonneau P, McManus J.J, Temperature-Dependent Interactions Explain Normal and Inverted Solubility in a γD-Crystallin Mutant, Biophysical Journal, 117, (5), 2019, p930 - 937
Emma McGrath, Dieter Waschbüsch, Brian M. Baker & Amir R. Khan, LRRK2 binds to the Rab32 subfamily in a GTPdependent manner via its armadillo domain, Small GTPases, 2019
WaschbÃŒsch, D. and HÃŒbel, N. and Ossendorf, E. and Lobbestael, E. and Baekelandt, V. and Lindsay, A.J. and McCaffrey, M.W. and Khan, A.R. and Barnekow, A., Rab32 interacts with SNX6 and affects retromer-dependent Golgi trafficking, PLoS ONE, 14, (1), 2019
Altan I, Khan A.R, James S, Quinn M.K, McManus J.J, Charbonneau P, Using Schematic Models to Understand the Microscopic Basis for Inverted Solubility in ?D-Crystallin, Journal of Physical Chemistry B, 123, (47), 2019, p10061 - 10072
Garg, R.R. and Jackson, C.B. and Rahman, M.M. and Khan, A.R. and Lewin, A.S. and McFadden, G., Myxoma virus M013 protein antagonizes NF-κB and inflammasome pathways via distinct structural motifs, Journal of Biological Chemistry, 294, (21), 2019, p8480-8489
Guagnini, F. and Antonik, P.M. and Rennie, M.L. and O'Byrne, P. and Khan, A.R. and Pinalli, R. and Dalcanale, E. and Crowley, P.B., Cucurbit[7]uril-Dimethyllysine Recognition in a Model Protein, Angewandte Chemie - International Edition, 57, (24), 2018, p7126-7130
Taglauer, E.S. and Artemiuk, P.A. and Hanscom, S.R. and Lindsay, A.J. and Wuebbolt, D. and Breathnach, F.M. and Tully, E.C. and Khan, A.R. and McCaffrey, M.W., Rab11 family expression in the human placenta: Localization at the maternal-fetal interface, PLoS ONE, 12, (9), 2017
Nounamo B, Li Y, O'Byrne P, Kearney A.M, Khan A, Liu J, An interaction domain in human SAMD9 is essential for myxoma virus host-range determinant M062 antagonism of host anti-viral function, Virology, 503, 2017, p94 - 102
Mulvaney E.P, O'Meara F, Khan A.R, O'Connell D.J, Kinsella B.T, Identification of α-helix 4 (α4) of Rab11a as a novel Rab11-binding domain (RBD): Interaction of Rab11a with the Prostacyclin Receptor, Biochimica et Biophysica Acta - Molecular Cell Research, 1864, (10), 2017, p1819 - 1832
N Willis-Fox, A. Gutacker, M.P. Browne, A.R. Khan, M.E.G.Lyons, U. Scherf, R.C. Evans, Selective recohnition of biologically important anions using a diblock polyfluorene-polythiophene conjugated polyelectrolyte, Polymer Chemistry, 8, 2017, p7151 - 7159
Oliveira T, Sharkey M.A, Engel P.C, Khan A.R, Crystal structure of a chimaeric bacterial glutamate dehydrogenase, Acta Crystallographica Section:F Structural Biology Communications, 72, 2016, p462 - 466
Lall, P., Lindsay, A.J., Hanscom, S., (...), McCaffrey, M.W., Khan, A.R., Structure-function analyses of the interactions between Rab11 and Rab14 small GTPases with their shared effector Rab coupling protein (RCP), Journal of Biological Chemistry, 290, (30), 2015, 18817-18832
Lall, P., Horgan, C.P., Oda, S., (...), McCaffrey, M.W., Khan, A.R., Structural and functional analysis of FIP2 binding to the endosome-localised Rab25 GTPase, Biochimica et Biophysica Acta - Proteins and Proteomics , 1834, (12), 2013, p2679-2690
Stack, J., Hurst, T.P., Flannery, S.M., (...), Khan, A.R., Bowie, A.G. , Poxviral protein A52 stimulates p38 mitogen-activated protein kinase (MAPK) activation by causing tumor necrosis factor receptor-associated factor 6 (TRAF6) self-association leading to transforming growth factor β-activated kinase 1 (TAK1) recruitment, Journal of Biological Chemistry, 288, (47), 2013, p33642-33653
Schmidt A.G, Xu H, Khan A.R, O'Donnell T, Khurana S, King L.R, Manischewitz J, Golding H, Suphaphiphat P, Carfi A, Settembre E.C, Dormitzer P.R, Kepler T.B, Zhang R, Moody M.A, Haynes B.F, Liao H.-X, Shaw D.E, Harrison S.C, Preconfiguration of the antigen-binding site during affinity maturation of a broadly neutralizing influenza virus antibody, Proceedings of the National Academy of Sciences of the United States of America, 110, (1), 2013, p264 - 269
Franklin, E., Khan, A.R., Poxvirus antagonism of innate immunity by Bcl-2 fold proteins, Journal of Structural Biology, 181, (1), 2013, p1-10
Khan AR, Oligomerization of rab/effector complexes in the regulation of vesicle trafficking., Progress in molecular biology and translational science, 117, 2013, p579-614
Lindsay A.J, Jollivet F, Horgan C.P, Khan A.R, Raposo G, McCaffrey M.W, Goud B, Identification and characterization of multiple novel Rab-myosin Va interactions, Molecular Biology of the Cell, 24, (21), 2013, p3420 - 3434
Stack J, Hurst TP, Flannery SM, Brennan K, Rupp S, Oda S, Khan AR, Bowie AG, Poxviral protein A52 stimulates p38 mitogen-activated protein kinase (MAPK) activation by causing tumor necrosis factor receptor-associated factor 6 (TRAF6) self-association leading to transforming growth factor ß-activated kinase 1 (TAK1) recruitment., The Journal of biological chemistry, 288, (47), 2013, p33642-53
Khan, A.R., Ménétrey, J., Structural biology of arf and rab GTPases' effector recruitment and specificity, Structure , 21, (8), 2013, p1284-1297
Sharkey MA, Oliveira TF, Engel PC, Khan AR, Structure of NADP(+)-dependent glutamate dehydrogenase from Escherichia coli--reflections on the basis of coenzyme specificity in the family of glutamate dehydrogenases., The FEBS journal, 280, (18), 2013, p4681-92
McGovern, R.E., Fernandes, H., Khan, A.R., Power, N.P., Crowley, P.B., Protein camouflage in cytochrome c-calixarene complexes, Nature Chemistry, 4, (7), 2012, p527-533
Fernandes, H., Franklin, E., Jollivet, F., Bliedtner, K., Khan, A.R., Mapping the interactions between a RUN domain from DENND5/Rab6IP1 and sorting nexin 1., PloS one, 7, (4), 2012, pe35637
Tânia Oliveira, Santosh Panjikar, John B. Carrigan, Muaawia Hamza, Paul C. Engel, Amir R. Khan, Crystal Structure of NAD-dependent Peptoniphilus Asaccharolyticus Glutamate Dehydrogenase Reveals Determinants of Cofactor Specificity, Journal of Structural Biology, 177, (2), 2012, p543-552
Jin, Y., Sultana, A., Gandhi, P., Franklin, E., Hamamoto, S., Khan, A.R., Munson, M., (...), Weisman, L.S., Myosin V transports secretory vesicles via a Rab GTPase cascade and interaction with the exocyst complex, Developmental Cell, 21, (6), 2011, p1156-1170
Fernandes H, Franklin E, Khan AR, Crystallization of an engineered RUN domain of Rab6-interacting protein 1/DENND5., Acta Crystallographica. Section F, Structural Biology and Crystallization Communications, 67, (Pt 5), 2011, p556-60
Shun-ichiro Oda, Edward Franklin, Amir R. Khan, Poxvirus A46 protein binds to TIR domain-containing Mal/TIRAP via an a-helical sub-domain, Molecular Immunology, 48, 2011, p2144 - 2150
Fernandes, H, Franklin, E, Khan, AR, Crystallization of an engineered RUN domain of Rab6-interacting protein 1/DENND5, ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS, 67, 2011, p556-560
Sultana, A., Jin, Y., Dregger, C., Franklin, E., Weisman, L.S., Khan, A.R., The activation cycle of Rab GTPase Ypt32 reveals structural determinants of effector recruitment and GDI binding, FEBS Letters, 585, (22), 2011, 3520-3527
Tânia F. Oliveira, Edward Franklin, José P. Afonso, Amir R. Khan, Neil J. Oldham, Inês A. C. Pereira and Margarida Archer, Structural insights into dissimilatory sulfite reductases: structure of desulforubidin from Desulfomicrobium norvegicum, Frontiers in Microbial Physiology and Metabolism, 2, (71), 2011
Oliveira, T.F., Carrigan, J.B., Hamza, M.A., Sharkey, M.A., Engel, P.C., Khan, A.R., Crystallization and preliminary structural analyses of glutamate dehydrogenase from Peptoniphilus asaccharolyticus, Acta Crystallographica Section F: Structural Biology and Crystallization Communications, 66, (5), 2010, p523-526
Nagle PS, Quinn SJ, Kelly JM, O'Donovan DH, Khan AR, Rodriguez F, Nguyen B, Wilson WD, Rozas I, Understanding the DNA binding of novel non-symmetrical guanidinium/2-aminoimidazolinium derivatives., Organic & Biomolecular chemistry, 8, (24), 2010, p5558-67
Crowley, P.B., Matias, P.M., Khan, A.R., Roessle, M., Svergun, D.I., Metal-mediated self-assembly of a β-sandwich protein, Chemistry - A European Journal , 15, (46), 2009, p12672-12680
Fernandes, H., Franklin, E., Recacha, R., Houdusse, A., Goud, B., Khan, A.R., Structural aspects of Rab6-effector complexes, Biochemical Society Transactions, 37, (5), 2009, p1037-1041
Shun-ichiro Oda, Martina Schroder, Amir R. Khan, Structural Basis for Targeting of Human RNA Helicase DDX3 by Poxvirus Protein K7, Structure (Cell Press), 17, 2009, p1528 - 1537
Kalverda AP, Thompson GS, Vogel A, Schröder M, Bowie AG, Khan AR & Homans SW, Poxvirus K7 protein adopts a Bcl-2 fold: Biochemical mapping of its interactions with human DEAD box RNA helicase DDX3., Journal of Molecular Biology, 385, (3), 2009, p843-853
Recacha R, Boulet A, Jollivet F, Monier S, Houdusse A, Goud B & Khan AR , Structural basis for recruitment of Rab6-Interacting Protein 1 to Golgi via a RUN domain., Structure, 17, (1), 2009, p21-30
Horgan CP, Oleksy1 A, Alexander V. Zhdanov AV, Lall PY, Ian J. White, Khan AR, Futter CE, McCaffrey JG & McCaffrey MW, Rab11-FIP3 is critical for the structural integrity of the endosomal-recycling compartment., Traffic, 8, (1), 2007, p414-430
Khor CC, Chapman SJ, Vannberg FO, Dunne A, Murphy C, Ling EY, Frodsham AJ, Walley AJ, Kyrieleis O, Khan A, Aucan C, Segal S, Moore CE, Knox K, Campbell SJ, Lienhardt C, Scott A, Aaby P, Sow OY, Grignani RT, Sillah J, Sirugo G, Peshu N, Williams TN, Maitland K, Davies RJ, Kwiatkowski DP, Day NP, Yala D, Crook DW, Marsh K, Berkley JA, O'Neill LA, Hill AV., A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis., Nature Genetics, 39, (4), 2007, p523-8
Jagoe WN, Jackson SR, Lindsay AJ, McCaffrey MW & Khan AR, Purification, crystallization, and preliminary X-ray diffraction studies of Rab11 in complex with Rab11-FIP2, Acta Crystallogr Sect F Struct Biol Cryst Commun. , 62, (7), 2006, p692 - 694
Jagoe WN, Lindsay AJ, Read RJ, McCoy AJ, McCaffrey MW & Khan AR, Crystal structure of Rab11 in complex with Rab11 Family Interacting Protein 2, Structure (Cell Press), 14, (8), 2006, p1273 - 1283
Chen M, Stafford W, Diedrich G, Khan AR and Bouvier M, A characterization of the lumenal region of human tapasin reveals the presence of two structural domains., Biochemistry, 41, (49), 2002, p14539 - 14545
Khan A.R, Baker B.M, Ghosh P, Biddison W.E, Wiley D.C, Erratum: The stucture and stability of an HLA-A*0201/octameric tax peptide complex with an empty conserved peptide-N-terminal binding site (Journal of Immunology (2000) 164 (6398-6405)), Journal of Immunology, 165, (7), 2000, p4141-
Khan A.R, Baker B.M, Ghosh P, Biddison W.E, Wiley D.C, The structure and stability of an HLA-A*0201/octameric tax peptide complex with an empty conserved peptide-N-terminal binding site, Journal of Immunology, 164, (12), 2000, p6398 - 6405
Khan A.R, Khazanovich-Bernstein N, Bergmann E.M, James M.N.G, Structural aspects of activation pathways of aspartic protease zymogens and viral 3C protease precursors, Proceedings of the National Academy of Sciences of the United States of America, 96, (20), 1999, p10968 - 10975
Khan AR, Khazanovich-Bernstein N, Bergmann EM & James MNG , Structural aspects of the activation pathways of aspartic protease zymogens and viral 3C protease zymogens. , Proc Natl Acad Sci USA , 96, (20), 1999, p10968 - 10975
Khan AR, Parrish JC, Fraser ME, Smith WW, Bartlett PA & James MNG, Lowering the entropic barrier for binding conformationally flexible inhibitors to enzymes. , Biochemistry, 37, (48), 1998, p16839 - 16845
Crystallographic studies of an activation intermediate of human gastricsin. in, editor(s)MNG James , The Aspartic Proteinases: Retroviral and Cellular Enzymes , New York, Plenum Press, 1998, pp265 - 270., [Amir Khan]
Mark BL, Wasney GA, Salo T, Khan AR, Cao Z, Robbins PW, James MNG & Triggs-Laine BL , Structural and functional characterization of Streptomyces plicatus Beta-N-acetylhexosaminidase by comparative molecular modelling and site-directed mutagenesis, Journal of Biological Chemistry , 273, (31), 1998, p19618 - 19624
Khan AR & James MNG , Molecular mechanisms for the conversion of zymogens to active proteolytic enzymes, Protein Science, 7, (4), 1998, p815 - 836
Khan AR, Johnson KA, Braam J & James MNG, Comparative molecular modelling of the three-dimensional structure of calmodulin-related TCH2 protein from Arabidopsis, Proteins: Structure, Function and Genetics , 27, (1), 1997, p144 - 153
Khan, A.R., Chernaia, M.M., Tarasova, N.I. , Structure of folding intermediate during activation of an aspartic proteinase zymogen, FASEB Journal, 11, (9), 1997, pA1396
Khan AR, Cherney MM, Tarasova NI & James MNG , Structural characterization of activation 'intermediate 2' on the pathway to human gastricsin, Nature Structural Biology , 4, (12), 1997, p1010 - 1015
Williams KA, Glibowicka M, Li Z, Li H, Khan AR, Chen YM, Wang J, Marvin DA & Deber CM, Role of small residues in filamentous phage packing. , Journal of Molecular Biology , 252, (1), 1995, p6 - 14
Khan AR & Deber CM, An engineered disulfide bridge in the transmembrane region of phage M13 coat protein stabilizes the omega-helical dimer., Biochemical and Biophysical Research Communications , 206, (1), 1995, p230 - 237
Williams K.A, Glibowicka M, Li Z, Li H, Khan A.R, Chen Y.M.Y, Wang J, Marvin D.A, Deber C.M, Packing of Coat Protein Amphipathic and Transmembrane Helices in Filamentous Bacteriophage M13: Role of Small Residues in Protein Oligomeriza tion, Journal of Molecular Biology, 252, (1), 1995, p6 - 14
Khan AR, Williams KA, Boggs JM & Deber CM , Accessibility and dynamics of viable Cys mutants of phage IKe and M13 major coat proteins, Biochemistry, 34, (38), 1995, p12388 - 12397
Deber CM, Khan AR, Li Z, Joensson C, Glibowicka M & Wang J, Val to Ala mutations selectively alter helix-helix packing in the transmembrane segment of phage M13 coat protein, Proc Natl Acad Sci USA, 90, (20), 1993, p11648 - 11652
Research Expertise
Description
Our lab is interested in the molecular mechanisms that underpin human health and disease. We exploit numerous biochemical, biophysical and structural techniques to enable a visualization of the 3-D structure of proteins signaling complexes. With the advent of 3-D prediction algorithms such as AlphaFold, our toolbox for understanding cellular processes at the molecular level has greatly expanded. We have a particular interest in the molecular basis for inherited forms of Parkinson"s disease. The autosomal dominant gene LRRK2 codes for a protein called LRRK2 kinase, which acquires enhanced activity and leads to neuronal cell death. LRRK2 phosphorylates its substrates, Rab GTPases, and dramatically alters cellular homeostasis. We are trying to understand this signaling pathway with a view to identifying new routes for therapeutics to treat the disease.Projects
- Title
- LRRK2 Control of Membrane Trafficking in Health and Disease
- Summary
- The most common cause of inherited Parkinson"s disease is a mutation in Leucine-Rich Repeat Kinase 2 (LRRK2). LRRK2 is implicated in numerous cellular processes including autophagy, mitochondrial dynamics, and ciliogenesis. Despite its importance there is little structural information on LRRK2 signaling pathways. In 2016, Rab GTPases were identified as the first bona fide substrates of LRRK2. Rabs are molecular switches that localize to subcellular compartments and regulate membrane trafficking through recruitment of cytosolic effector proteins. LRRK2 is an effector of Rab29 and is recruited to Golgi where it phosphorylates Rab8a and Rab10. Here we will investigate the molecular basis for the LRRK2 and Rab signaling cascade using X-ray crystallography. The structural basis for Rab29 binding to LRRK2 will be determined. Downstream pathways involving the interactions between phosphorylated Rab8a/10 and phospho-specific effector proteins will be studied using structural and biophysical techniques. Finally, we will investigate the structure and function of PPM1H phosphatase which counters LRRK2 activation by dephosphorylating Rab GTPases. Reversible phosphorylation of Rab GTPases has emerged as a critical regulatory mechanism that is associated with LRRK2 signaling cascades. The project will address fundamental questions on the physiological role of LRRK2 through its regulatory and substrate Rab GTPases.
- Funding Agency
- Science Foundation Ireland
Recognition
Awards and Honours
Cyril M. Kay Book Prize in Biochemistry University of Alberta
Studentship, Medical Research Council of Canada
Student Travel Award, American Crystallographic Association St. Louis, MI
Finn Wold Travel Award, Eleventh Symposium of the Protein Society, Boston, MA
Dissertation Fellowship, University of Alberta
Graduate Student Poster Prize, CFBS Annual Meeting Edmonton, Alberta
Fellowship, Human Frontiers Science Program
Fellowship, Centre National de la Recherche Scientifique (CNRS), France
Fellowship, Canadian Institutes of Health Research (CIHR)
Research Grant, Scientific Investigator Programme, Science Foundation Ireland