Howard Ronald Kaback

Howard Ronald Kaback was an American Biochemist, known for Kabackosomes, the cell-free membrane transport vesicles. He was the brother of Michael M. Kaback, pediatrician and human geneticist, who developed a screening program to detect and prevent Tay–Sachs disease, a rare and fatal genetic disorder most common in Ashkenazi Jews.[1]

H. Ronald Kaback
Born (1936-06-05) June 5, 1936
Philadelphia, United States of America
DiedDecember 20, 2019
Los Angeles, California
Other namesRon Kaback
OccupationMolecular Biologist, Biochemist
Years active1960 – 2019
Spouse(s)Molly Kaback
AwardsRosenstiel Award (1974)
Member of the American Academy of Arts and Sciences (1986)
Member of the National Academy of Sciences (1987)
Anatrace Membrane Protein Award (2007)
Distinguished Alumni Achievement Award (2009)
Peter Mitchell Memorial Medal (2012)
Websitehttp://149.142.237.181/H.R._Kaback.html

Biography

Prof. H. Ronald Kaback was born in Philadelphia, Pennsylvania. He earned his BS at Haverford College in 1958 and his MD at The Einstein College of Medicine in 1962.[2] He interned at the Bronx Municipal Hospital Center in Pediatrics and did pre- and postdoctoral research at Einstein College in the laboratory of Adele B. Kostellow. In 1964 he moved to National Heart Institute to the laboratory of Earl R. Stadtman.

In 1970, he joined the Roche Institute of Molecular biology in Nutley, NJ where he later became Head of Biochemistry. In 1989 he became an Investigator of the Howard Hughes Medical Institute and Professor of Physiology and Microbiology, Immunology & Molecular Genetics, as well as a member of the Molecular Biology Institute at the University of California Los Angeles.[3]

Career

Ronald Kaback became interested in membrane transport at a time when studies on biological membranes were in their infancy, and in the early phase of his career, he developed a cell-free membrane system to study active transport. The system consisted of osmotically sealed membrane vesicles of defined orientation (right-side-out) that catalyze active transport essentially as well as intact cells, but lack subsequent metabolism of the solutes accumulated.[4] These vesicles were dubbed Kabackosomes by the Dutch scientist Wilhelmus N. Konings, Kaback's close friend and early collaborator. In addition to transforming the field of transport from phenomenology to biochemistry, this seminal development caused him to forego the practice of pediatrics for a career in basic science. The use of membrane vesicles from various sources has become a standard tool for testing models and performing hypothesis-driven research.

Kaback demonstrated quantitatively that an electrochemical H+ gradient is the immediate driving force for accumulation of many different solutes. Peter Mitchell who conceived and formulated the ‘’Chemiosmotic Hypothesis’’ considered these findings to be the most conclusive experimental support for the Hypothesis with respect to membrane transport. Kaback extended his interest to the molecular mechanism of membrane transport by focusing on the lactose permease of Escherichia coli (LacY; aka the lactose/H+ symporter), which is now a paradigm for the Major Facilitator Superfamily, arguably the largest group of membrane transport proteins.[5][6] With the emergence of molecular biology, he and his colleagues pioneered Cysteine-Scanning Mutagenesis in combination with chemical modification, as well as a battery of site-directed biophysical/biochemical techniques to demonstrate almost incontrovertibly that LacY functions by a mechanism involving alternating access of sugar- and proton-binding sites to either side of the membrane.[7] This general experimental approach is recognized today and has become a standard tool for membrane protein research. Without a crystal structure, Kaback and colleagues succeeded in using the approach to obtain essential information about helix packing, the organization of the sugar-binding site, and the residues involved in H+ translocation and coupling.[8][9][10]

He and his colleagues then obtained an X-ray crystal structure of LacY, an essential step towards understanding the molecular mechanism, which has had important impact on the field of membrane transport.[11] Ronald Kaback gives lectures regularly at international meetings.[12] His laboratory continues to extend studies on the evolution[13] and mechanism[14][15] of LacY and other symport proteins.[16][17]

Awards and recognitions
  • Lewis S. Rosenstiel Award (1973)[18]
  • Member of the American Academy of Arts and Sciences (1986)[19]
  • Member of the National Academy of Sciences (1987)[20]
  • Anatrace Membrane Protein Award (2007)[21]
  • Distinguished Alumni Achievement Award (2009)
  • Peter Mitchell Memorial Medal (2012)

Selected publications

The results of Kaback's studies are described in over 450 publications[21] in peer-reviewed scientific journals. His research is also chronicled in textbooks, reference books and teaching materials in many languages for both undergraduate and graduate teaching.

References
  1. Kaback, Michael (2001). Tay–Sachs Disease. Academic Press. ISBN 0120176440.
  2. "Ronald Kaback M.D. | David Geffen School of Medicine at UCLA". People.healthsciences.ucla.edu. Retrieved 2014-05-14.
  3. Kaback, Howard Ronald (1989). "Professor- UCLA".
  4. Kaback, HR (6 December 1974). "Transport studies in bacterial membrane vesicles". Science. 186 (4167): 882–92. Bibcode:1974Sci...186..882K. doi:10.1126/science.186.4167.882. PMID 4620043.
  5. Kaback, Howard Ronald; Smirnova I; Kasho V. (2011). "Lactose Permease and the Alternating Access Mechanism". Biochemistry. 50 (45): 9684–9693. doi:10.1021/bi2014294. PMC 3210931. PMID 21995338.
  6. Madej, M. Gregor; Kaback, H. Ronald (2014). "The Life and Times of Lac Permease: Crystals Ain't Everything, but They Certainly Do Help". In Krämer, R.; Ziegler, Ch. (eds.). Membrane Transport Mechanism 3D Structure and Beyond. Heidelberg, New York, Dordrecht, London: Springer. pp. 121–158. ISBN 978-3-642-53838-4.
  7. Kaback, Howard Ronald; Frillingos S; Sahin-Toth M; Wu J. (1998). "Cys-scanning mutagenesis: a novel approach to structure function relationships in polytopic membrane proteins". FASEB J. 12 (13): 1281–99. doi:10.1096/fasebj.12.13.1281. PMID 9761772. S2CID 19339881.
  8. Sahin-Toth, M; Kaback, HR (22 May 2001). "Arg-302 facilitates deprotonation of Glu-325 in the transport mechanism of the lactose permease from Escherichiacoli". Proceedings of the National Academy of Sciences of the United States of America. 98 (11): 6068–73. Bibcode:2001PNAS...98.6068S. doi:10.1073/pnas.111139698. PMC 33423. PMID 11353849.
  9. Kwaw, I; Zen, KC; Hu, Y; Kaback, HR (4 September 2001). "Site-directed sulfhydryl labeling of the lactose permease of Escherichia coli: helices IV and V that contain the major determinants for substrate binding". Biochemistry. 40 (35): 10491–9. doi:10.1021/bi010866x. PMID 11523990.
  10. Guan, L; Weinglass, AB; Kaback, HR (7 September 2001). "Helix packing in the lactose permease of Escherichia coli: localization of helix VI". Journal of Molecular Biology. 312 (1): 69–77. doi:10.1006/jmbi.2001.4933. PMID 11545586.
  11. Kaback, Howard Ronald; Abramson J; Smimova I; Kasho V; Verner G; Iwata S. (2003). "Structure and mechanism of the lactose permease of Escherichia coli". Science. 301 (5633): 610–5. Bibcode:2003Sci...301..610A. doi:10.1126/science.1088196. PMID 12893935. S2CID 36908983.
  12. Hopkin, Karen (May 1, 2011). "Making the Gradient". The Scientist. 25 (5).
  13. Madej, MG; Dang, S; Yan, N; Kaback, HR (9 April 2013). "Evolutionary mix-and-match with MFS transporters". Proceedings of the National Academy of Sciences of the United States of America. 110 (15): 5870–4. Bibcode:2013PNAS..110.5870M. doi:10.1073/pnas.1303538110. PMC 3625355. PMID 23530251.
  14. Kaback, HR (3 February 2015). "A chemiosmotic mechanism of symport". Proceedings of the National Academy of Sciences of the United States of America. 112 (5): 1259–64. Bibcode:2015PNAS..112.1259K. doi:10.1073/pnas.1419325112. PMC 4321259. PMID 25568085.
  15. Bazzone, A; Madej, MG; Kaback, HR; Fendler, K (2016). "pH Regulation of Electrogenic Sugar/H+ Symport in MFS Sugar Permeases". PLOS ONE. 11 (5): e0156392. Bibcode:2016PLoSO..1156392B. doi:10.1371/journal.pone.0156392. PMC 4882079. PMID 27227677.
  16. Ethayathulla, AS; Yousef, MS; Amin, A; Leblanc, G; Kaback, HR; Guan, L (2014). "Structure-based mechanism for Na(+)/melibiose symport by MelB". Nature Communications. 5: 3009. Bibcode:2014NatCo...5.3009E. doi:10.1038/ncomms4009. PMC 4026327. PMID 24389923.
  17. Madej, MG; Sun, L; Yan, N; Kaback, HR (18 February 2014). "Functional architecture of MFS D-glucose transporters". Proceedings of the National Academy of Sciences of the United States of America. 111 (7): E719-27. Bibcode:2014PNAS..111E.719M. doi:10.1073/pnas.1400336111. PMC 3932877. PMID 24550316.
  18. "Rosenstiel Award Past Winners". Rose.brandeis.edu. Archived from the original on 2014-05-15. Retrieved 2014-05-14.
  19. List of Members 1780–present (PDF, 669 kB); American Academy of Arts and Sciences (amacad.org); retrieved, 29 December 2019
  20. "H. Ronald Kaback". Nasonline.org. 1993-09-19. Retrieved 2019-12-29.
  21. "UCLA Molecular, Cellular and Integrative Physiology Interdisciplinary Program". Mcip.ucla.edu. Archived from the original on 2014-05-15. Retrieved 2014-05-14.
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