Brian Kobilka

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Brian Kobilka
Brian Kobilka 361726 by Christopher Michel 6-20-24.jpg
Brian Kobilka at Stanford in 2024
Born
Brian Kent Kobilka

(1955-05-30) May 30, 1955 (age 69)
Little Falls, Minnesota, United States
Alma mater University of Minnesota Duluth (BS)
Yale University (MD)
Awards Nobel Prize in Chemistry (2012)
Scientific career
Fields Crystallography
Institutions Stanford University, Duke University
Academic advisors Robert Lefkowitz

Brian Kent Kobilka (born May 30, 1955) [1] is an American physiologist and a recipient of the 2012 Nobel Prize in Chemistry with Robert Lefkowitz for discoveries that reveal the workings of G protein-coupled receptors. He is currently a professor in the department of Molecular and Cellular Physiology at Stanford University School of Medicine. He is also a co-founder of ConfometRx, a biotechnology company focusing on G protein-coupled receptors. He was named a member of the National Academy of Sciences in 2011.

Contents

Early life

Kobilka attended St. Mary's Grade School in Little Falls, Minnesota, a part of the Roman Catholic Diocese of Saint Cloud. [2] He then graduated from Little Falls High School. He received a Bachelor’s Degree in Biology and Chemistry from the University of Minnesota Duluth, and earned his M.D., cum laude , from Yale University School of Medicine. Following the completion of his residency in internal medicine at Washington University in St. Louis School of Medicine's Barnes-Jewish Hospital. Kobilka worked in research as a postdoctoral fellow under Robert Lefkowitz at Duke University, where he started work on cloning the β2-adrenergic receptor. Kobilka moved to Stanford in 1989. [3] He was a Howard Hughes Medical Institute (HHMI) investigator from 1987 to 2003. [4]

Research

Kobilka in Stockholm 2012 Brian Kobilka 1 2012.jpg
Kobilka in Stockholm 2012

Kobilka is best known for his research on the structure and activity of G protein-coupled receptors (GPCRs); in particular, work from Kobilka's laboratory determined the molecular structure of the β2-adrenergic receptor. [5] [6] [7] [8] This work has been highly cited by other scientists because GPCRs are important targets for pharmaceutical therapeutics, but notoriously difficult to work with in X-ray crystallography. [9] Before, rhodopsin was the only G-protein coupled receptor where the structure had been determined at high resolution. The β2-adrenergic receptor structure was soon followed by the determination of the molecular structure of several other G-protein coupled receptors. [10]

Kobilka is the 1994 recipient of the American Society for Pharmacology and Experimental Therapeutics John J. Abel Award in Pharmacology. [11] His GPCR structure work was named "runner-up" for the 2007 "Breakthrough of the Year" award from Science . [12] The work was, in part, supported by Kobilka's 2004 Javits Neuroscience Investigator Award [13] from the National Institute of Neurological Disorders and Stroke. [14] He received the 2012 Nobel Prize in Chemistry with Robert Lefkowitz for his work on G protein-coupled receptors. [15] [16] In 2017, Kobilka received the Golden Plate Award of the American Academy of Achievement. [17]

As part of Shenzhen’s 13th Five-Year Plan funding research in emerging technologies and opening "Nobel laureate research labs", [18] in 2017 he opened the Kobilka Institute of Innovative Drug Discovery at the Chinese University of Hong Kong, Shenzhen in Southern China. [19]

Personal life

Kobilka is from Little Falls in central Minnesota. Both his grandfather Felix J. Kobilka (1893–1991) and his father Franklyn A. Kobilka (1921–2004) were bakers and natives of Little Falls, Minnesota. [20] [21] [22] Kobilka's grandmother, Isabelle Susan Kobilka (née Medved, 1891–1980), belonged to the Medved and Kiewel families of Prussian immigrants, who from 1888 owned the historical Kiewel brewery in Little Falls. His mother is Betty L. Kobilka (née Faust, b. 1930).

Kobilka met his wife Tong Sun Thian, a Malaysian-Chinese woman, [23] at the University of Minnesota Duluth. They have two children, Jason and Megan Kobilka. [20] [24]

Related Research Articles

<span class="mw-page-title-main">G protein-coupled receptor</span> Class of cell surface receptors coupled to G-protein-associated intracellular signaling

G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. They are coupled with G proteins. They pass through the cell membrane seven times in the form of six loops of amino acid residues, which is why they are sometimes referred to as seven-transmembrane receptors. Ligands can bind either to the extracellular N-terminus and loops or to the binding site within transmembrane helices. They are all activated by agonists, although a spontaneous auto-activation of an empty receptor has also been observed.

<span class="mw-page-title-main">G protein</span> Type of proteins

G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their activity is regulated by factors that control their ability to bind to and hydrolyze guanosine triphosphate (GTP) to guanosine diphosphate (GDP). When they are bound to GTP, they are 'on', and, when they are bound to GDP, they are 'off'. G proteins belong to the larger group of enzymes called GTPases.

Functional selectivity is the ligand-dependent selectivity for certain signal transduction pathways relative to a reference ligand at the same receptor. Functional selectivity can be present when a receptor has several possible signal transduction pathways. To which degree each pathway is activated thus depends on which ligand binds to the receptor. Functional selectivity, or biased signaling, is most extensively characterized at G protein coupled receptors (GPCRs). A number of biased agonists, such as those at muscarinic M2 receptors tested as analgesics or antiproliferative drugs, or those at opioid receptors that mediate pain, show potential at various receptor families to increase beneficial properties while reducing side effects. For example, pre-clinical studies with G protein biased agonists at the μ-opioid receptor show equivalent efficacy for treating pain with reduced risk for addictive potential and respiratory depression. Studies within the chemokine receptor system also suggest that GPCR biased agonism is physiologically relevant. For example, a beta-arrestin biased agonist of the chemokine receptor CXCR3 induced greater chemotaxis of T cells relative to a G protein biased agonist.

<span class="mw-page-title-main">Beta-1 adrenergic receptor</span> Protein-coding gene in the species Homo sapiens

The beta-1 adrenergic receptor, also known as ADRB1, can refer to either the protein-encoding gene or one of the four adrenergic receptors. It is a G-protein coupled receptor associated with the Gs heterotrimeric G-protein that is expressed predominantly in cardiac tissue. In addition to cardiac tissue, beta-1 adrenergic receptors are also expressed in the cerebral cortex.

<span class="mw-page-title-main">Beta-2 adrenergic receptor</span> Mammalian protein found in humans

The beta-2 adrenergic receptor, also known as ADRB2, is a cell membrane-spanning beta-adrenergic receptor that binds epinephrine (adrenaline), a hormone and neurotransmitter whose signaling, via adenylate cyclase stimulation through trimeric Gs proteins, increases cAMP, and, via downstream L-type calcium channel interaction, mediates physiologic responses such as smooth muscle relaxation and bronchodilation.

<span class="mw-page-title-main">Arrestin</span> Family of proteins

Arrestins are a small family of proteins important for regulating signal transduction at G protein-coupled receptors. Arrestins were first discovered as a part of a conserved two-step mechanism for regulating the activity of G protein-coupled receptors (GPCRs) in the visual rhodopsin system by Hermann Kühn, Scott Hall, and Ursula Wilden and in the β-adrenergic system by Martin J. Lohse and co-workers.

<span class="mw-page-title-main">G protein-coupled receptor kinase</span> Family of protein kinases

G protein-coupled receptor kinases are a family of protein kinases within the AGC group of kinases. Like all AGC kinases, GRKs use ATP to add phosphate to Serine and Threonine residues in specific locations of target proteins. In particular, GRKs phosphorylate intracellular domains of G protein-coupled receptors (GPCRs). GRKs function in tandem with arrestin proteins to regulate the sensitivity of GPCRs for stimulating downstream heterotrimeric G protein and G protein-independent signaling pathways.

<span class="mw-page-title-main">G protein-coupled receptor kinase 2</span> Enzyme

G-protein-coupled receptor kinase 2 (GRK2) is an enzyme that in humans is encoded by the ADRBK1 gene. GRK2 was initially called Beta-adrenergic receptor kinase, and is a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinases that is most highly similar to GRK3(βARK2).

<span class="mw-page-title-main">Heterotrimeric G protein</span> Class of enzymes

Heterotrimeric G protein, also sometimes referred to as the "large" G proteins are membrane-associated G proteins that form a heterotrimeric complex. The biggest non-structural difference between heterotrimeric and monomeric G protein is that heterotrimeric proteins bind to their cell-surface receptors, called G protein-coupled receptors (GPCR), directly. These G proteins are made up of alpha (α), beta (β) and gamma (γ) subunits. The alpha subunit is attached to either a GTP or GDP, which serves as an on-off switch for the activation of G-protein.

<span class="mw-page-title-main">Robert Lefkowitz</span> American physician and biochemist

Robert Joseph Lefkowitz is an American physician and biochemist. He is best known for his discoveries that reveal the inner workings of an important family of G protein-coupled receptors, for which he was awarded the 2012 Nobel Prize for Chemistry with Brian Kobilka. He is currently an Investigator with the Howard Hughes Medical Institute as well as a James B. Duke Professor of Medicine and Professor of Biochemistry and Chemistry at Duke University.

G<sub>s</sub> alpha subunit Mammalian protein found in Homo sapiens

The Gs alpha subunit is a subunit of the heterotrimeric G protein Gs that stimulates the cAMP-dependent pathway by activating adenylyl cyclase. Gsα is a GTPase that functions as a cellular signaling protein. Gsα is the founding member of one of the four families of heterotrimeric G proteins, defined by the alpha subunits they contain: the Gαs family, Gαi/Gαo family, Gαq family, and Gα12/Gα13 family. The Gs-family has only two members: the other member is Golf, named for its predominant expression in the olfactory system. In humans, Gsα is encoded by the GNAS complex locus, while Golfα is encoded by the GNAL gene.

<span class="mw-page-title-main">Naltrindole</span> Chemical compound

Naltrindole is a highly potent, highly selective delta opioid receptor antagonist used in biomedical research. In May 2012 a paper was published in Nature with the structure of naltrindole in complex with the mouse δ-opioid G-protein coupled receptor, solved by X-ray crystallography.

<span class="mw-page-title-main">Alpha-2B adrenergic receptor</span> Protein-coding gene in the species Homo sapiens

The alpha-2B adrenergic receptor, is a G-protein coupled receptor. It is a subtype of the adrenergic receptor family. The human gene encoding this receptor has the symbol ADRA2B. ADRA2B orthologs have been identified in several mammals.

<span class="mw-page-title-main">GRK5</span> Protein-coding gene in the species Homo sapiens

G protein-coupled receptor kinase 5 is a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinases, and is most highly similar to GRK4 and GRK6. The protein phosphorylates the activated forms of G protein-coupled receptors to regulate their signaling.

<span class="mw-page-title-main">G beta-gamma complex</span>

The G beta-gamma complex (Gβγ) is a tightly bound dimeric protein complex, composed of one Gβ and one Gγ subunit, and is a component of heterotrimeric G proteins. Heterotrimeric G proteins, also called guanine nucleotide-binding proteins, consist of three subunits, called alpha, beta, and gamma subunits, or Gα, Gβ, and Gγ. When a G protein-coupled receptor (GPCR) is activated, Gα dissociates from Gβγ, allowing both subunits to perform their respective downstream signaling effects. One of the major functions of Gβγ is the inhibition of the Gα subunit.

<span class="mw-page-title-main">GPCR oligomer</span> Class of protein complexes

A GPCR oligomer is a protein complex that consists of a small number of G protein-coupled receptors (GPCRs). It is held together by covalent bonds or by intermolecular forces. The subunits within this complex are called protomers, while unconnected receptors are called monomers. Receptor homomers consist of identical protomers, while heteromers consist of different protomers.

FAUC50 is a covalent agonist of the β2 adrenoceptor. It has been used as a template to form covalent agonists for other receptors.

<span class="mw-page-title-main">Christopher G. Tate</span>

Christopher G. TateFRS is an English membrane protein biochemist and molecular biologist who works at the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK. Tate is known for his contributions to the understanding of G protein-coupled receptors.

Arun Kumar Shukla is an Indian structural biologist and the Joy-Gill Chair professor at the department of biological sciences and bioengineering at the Indian Institute of Technology, Kanpur. Known for his studies on G protein-coupled receptor, Shukla is a Wellcome Trust-DBT Intermediate Fellow and a recipient of the SwarnaJayanti Fellowship of the Department of Science and Technology. The Department of Biotechnology of the Government of India awarded him the National Bioscience Award for Career Development, one of the highest Indian science awards, for his contributions to biosciences, in 2017/18. He received the 2021 Shanti Swarup Bhatnagar Prize for Science and Technology in Biological Science. He was awarded the Infosys Prize 2023 in Life Sciences his outstanding contributions to the biology of G-protein coupled receptors (GPCRs).

<span class="mw-page-title-main">Jan Steyaert</span> Belgian bioengineer and molecular biologist

Jan Steyaert is a Belgian bioengineer and molecular biologist. He started his career as an enzymologist but the Steyaertlab is best known for pioneering work on (engineered) nanobodies for applications in structural biology, omics and drug design. He is full professor and teaches biochemistry at the Vrije Universiteit Brussel and Director of the VIB-VUB Center for Structural Biology, one of the Research Centers of the Vlaams Instituut voor Biotechnologie (VIB). He was involved in the foundation of three spin-off companies: Ablynx, Biotalys, and Confo Therapeutics.

References

  1. ↑ "BRIAN K. KOBILKA, MD". Tsinghua University School of Medicine. Archived from the original on 2012-12-16. Retrieved 2013-01-16.
  2. ↑ "Catholic scientist at Stanford shares Nobel Prize for work in chemistry". Catholic News Service. 2012-10-23. Archived from the original on 2013-02-15. Retrieved 2013-01-19.
  3. ↑ Nature Reviews Drug Discovery GPCR Questionnaire Participants (2004). "The state of GPCR research in 2004 : Nature Reviews Drug Discovery". Nature Reviews Drug Discovery. 3 (7). Nature: 577–626. doi:10.1038/nrd1458. PMID   15272499. S2CID   33620092 . Retrieved 2013-01-19.
  4. ↑ "Brian K. Kobilka, M.D." HHMI. Archived from the original on 2014-05-02. Retrieved 2013-01-19.
  5. ↑ "Cell Insights Could Bring Better Drugs". Forbes . Archived from the original on 2011-02-15. Retrieved 2013-01-23.
  6. ↑ Rasmussen SG, Choi HJ, Rosenbaum DM, Kobilka TS, Thian FS, Edwards PC, Burghammer M, Ratnala VR, Sanishvili R, Fischetti RF, Schertler GF, Weis WI, Kobilka BK (2007). "Crystal structure of the human β2-adrenergic G-protein-coupled receptor". Nature. 450 (7168): 383–7. Bibcode:2007Natur.450..383R. doi:10.1038/nature06325. PMID   17952055. S2CID   4407117.
  7. ↑ Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK, Stevens RC (2007). "High Resolution Crystal Structure of an Engineered Human β2-Adrenergic G protein-Coupled Receptor". Science. 318 (5854): 1258–65. Bibcode:2007Sci...318.1258C. doi:10.1126/science.1150577. PMC   2583103 . PMID   17962520.
  8. ↑ Rosenbaum DM, Cherezov V, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Yao XJ, Weis WI, Stevens RC, Kobilka BK (2007). "GPCR engineering yields high-resolution structural insights into β2-adrenergic receptor function". Science. 318 (5854): 1266–73. Bibcode:2007Sci...318.1266R. doi: 10.1126/science.1150609 . PMID   17962519. S2CID   1559802.
  9. ↑ ScienceWatch.com: "Interview with Brian Kobilka". Archived from the original on 2010-05-08. Retrieved 2008-10-16.
  10. ↑ Hanson, M. A.; Stevens, R. C. (2009). "Discovery of New GPCR Biology: One Receptor Structure at a Time". Structure. 17 (1): 8–14. doi:10.1016/j.str.2008.12.003. PMC   2813843 . PMID   19141277.
  11. ↑ "John J. Abel Award". ASPET. Retrieved 2013-01-24.
  12. ↑ "Kobilka's work recognized in magazine award". Stanford University. 2008-01-09. Retrieved 2013-01-24.
  13. ↑ "Javits Neuroscience Investigator Award Recognizes Eight Exemplary Scientists". National Institute of Neurological Disorders and Stroke (NINDS). 2004-11-10. Archived from the original on 2008-10-07. Retrieved 2013-01-24.
  14. ↑ "The Structure of an Important Drug Target Made Crystal Clear". National Institute of Neurological Disorders and Stroke (NINDS). 2007-12-05. Archived from the original on 2008-10-01. Retrieved 2013-01-24.
  15. ↑ Hotz, Robert Lee (October 10, 2012). "U.S. Scientists Win Chemistry Nobel". The Wall Street Journal Online. Retrieved October 10, 2012.
  16. ↑ "Americans Robert Lefkowitz and Brian Kobilka win 2012 Nobel Prize in chemistry". Daily News. AP. 10 October 2012. Retrieved 11 October 2012.
  17. ↑ "Golden Plate Awardees of the American Academy of Achievement". www.achievement.org. American Academy of Achievement.
  18. ↑ "Shenzhen Has 7 Nobel Prize Winners' Labs, 3 More Planned". That's Online. Retrieved 2021-03-15.
  19. ↑ "KOBILKA INSTITUTE OF INNOVATIVE DRUG DISCOVERY | CUHK-Shenzhen". lhs.cuhk.edu.cn. Retrieved 2021-03-15.
  20. 1 2 "Franklyn A. Kobilka, 83". ECM Publishers, Inc. 2004-03-16. Archived from the original on 2012-12-09. Retrieved 2013-01-16.
  21. ↑ Paul Walsh; Alejandra Matos (2012-10-11). "Little Falls bakery helps deliver a sweet reward: Nobel Prize". StarTribune. Retrieved 2013-01-16.
  22. ↑ "Social Security Death Index". Archived from the original on 2012-12-06. Retrieved 2012-10-10.
  23. ↑ 大馬華人女婿獲諾獎‧化學獎得主科比爾卡會煮豉油雞 (in Chinese). 星洲日報. 2012-10-11. Archived from the original on 2012-12-19. Retrieved 2013-01-16.
  24. ↑ Buchen, Lizzie (24 August 2011). "Cell signalling: It's all about the structure". Nature. 476 (7361): 387–390. Bibcode:2011Natur.476..387B. doi: 10.1038/476387a . PMID   21866135.

Publications

Awards
Preceded by Nobel Prize in Chemistry laureate
2012
With: Robert Lefkowitz 		Succeeded by
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