LRAT-specific domain facilitates vitamin A metabolism by domain swapping in HRASLS3

Golczak, Marcin; Sears, Avery E.; Kiser, Philip D.; Palczewski, Krzysztof

doi:10.1038/nchembio.1687

Title: LRAT-specific domain facilitates vitamin A metabolism by domain swapping in HRASLS3

Journal Article · Mon Nov 10 00:00:00 EST 2014 · Nature Chemical Biology

DOI:https://doi.org/10.1038/nchembio.1687· OSTI ID:1168504

Golczak, Marcin ^[1]; Sears, Avery E. ^[1]; Kiser, Philip D. ^[1]; Palczewski, Krzysztof ^[1]

Case Western Reserve Univ., Cleveland, OH (United States). School of Medicine. Cleveland Center for Membrane and Structural Biology. Dept. of Pharmacology

Cellular uptake of vitamin A, production of visual chromophore and triglyceride homeostasis in adipocytes depend on two representatives of the vertebrate N1pC/P60 protein family, lecithin:retinol acyltransferase (LRAT) and HRAS-like tumor suppressor 3 (HRASLS3). Both proteins function as lipid-metabolizing enzymes but differ in their substrate preferences and dominant catalytic activity. The mechanism of this catalytic diversity is not understood. In this paper, by using a gain-of-function approach, we identified a specific sequence responsible for the substrate specificity of N1pC/P60 proteins. A 2.2-Å crystal structure of the HRASLS3-LRAT chimeric enzyme in a thioester catalytic intermediate state revealed a major structural rearrangement accompanied by three-dimensional domain swapping dimerization not observed in native HRASLS proteins. Structural changes affecting the active site environment contributed to slower hydrolysis of the catalytic intermediate, supporting efficient acyl transfer. Finally, these findings reveal structural adaptation that facilitates selective catalysis and mechanism responsible for diverse substrate specificity within the LRAT-like enzyme family.

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Research Organization:: Case Western Reserve Univ., Cleveland, OH (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health (NIH) (United States)

Grant/Contract Number:: AC02-06CH11357; EY023948; EY009339; T32 GM007250; P41RR012408; P41GM103473

OSTI ID:: 1168504

Journal Information:: Nature Chemical Biology, Vol. 11, Issue 1; ISSN 1552-4450

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 38 works

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References (57)

Shape Complementarity at Protein/Protein Interfaces Lawrence, Michael C.; Colman, Peter M. Journal of Molecular Biology, Vol. 234, Issue 4 https://doi.org/10.1006/jmbi.1993.1648	journal	December 1993
Substrate specificities and mechanism in the enzymic processing of vitamin A into 11-cis-retinol Canada, Francisco J.; Law, Wing C.; Rando, Robert R. Biochemistry, Vol. 29, Issue 41 https://doi.org/10.1021/bi00493a026	journal	October 1990
Refinement of Macromolecular Structures by the Maximum-Likelihood Method Murshudov, G. N.; Vagin, A. A.; Dodson, E. J. Acta Crystallographica Section D Biological Crystallography, Vol. 53, Issue 3 https://doi.org/10.1107/S0907444996012255	journal	May 1997
Overview of the CCP 4 suite and current developments Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D. Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444910045749	journal	March 2011
Evolution and the origin of the visual retinoid cycle in vertebrates Kusakabe, Takehiro G.; Takimoto, Noriko; Jin, Minghao Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 364, Issue 1531 https://doi.org/10.1098/rstb.2009.0043	journal	October 2009
Early Onset Retinal Dystrophy Due to Mutations in LRAT : Molecular Analysis and Detailed Phenotypic Study Dev Borman, Arundhati; Ocaka, Louise A.; Mackay, Donna S. Investigative Opthalmology & Visual Science, Vol. 53, Issue 7 https://doi.org/10.1167/iovs.12-9548	journal	June 2012
A rapid and efficient purification method for recombinant annexin V for biophysical studies Burger, A.; Berendes, R.; Voges, D. FEBS Letters, Vol. 329, Issue 1-2 https://doi.org/10.1016/0014-5793(93)80185-W	journal	August 1993
Disruption of the Lecithin:Retinol Acyltransferase Gene Makes Mice More Susceptible to Vitamin A Deficiency Liu, Limin; Gudas, Lorraine J. Journal of Biological Chemistry, Vol. 280, Issue 48 https://doi.org/10.1074/jbc.m509643200	journal	September 2005
MolProbity: all-atom contacts and structure validation for proteins and nucleic acids B., Chen, Vincent; C., Richardson, David; S., Richardson, Jane The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/m2an-p252	text	January 2007
Different Active-Site Loop Orientation in Serine Hydrolases versus Acyltransferases Jiang, Yun; Morley, Krista L.; Schrag, Joseph D. ChemBioChem, Vol. 12, Issue 5 https://doi.org/10.1002/cbic.201000693	journal	February 2011
Lecithin:Retinol Acyltransferase Is Critical for Cellular Uptake of Vitamin A from Serum Retinol-binding Protein Amengual, Jaume; Golczak, Marcin; Palczewski, Krzysztof Journal of Biological Chemistry, Vol. 287, Issue 29 https://doi.org/10.1074/jbc.M112.353979	journal	May 2012
Principles of Fluorescence Spectroscopy Lakowicz, Joseph R. Springer New York, NY https://doi.org/10.1007/978-0-387-46312-4	book	January 2006
Expression, purification and biochemical characterization of the N-terminal regions of human TIG3 and HRASLS3 proteins Han, Byeong-Gu; Cho, Jea-Won; Cho, Young-Doo Protein Expression and Purification, Vol. 71, Issue 1 https://doi.org/10.1016/j.pep.2010.01.018	journal	May 2010
Origin and Evolution of Retinoid Isomerization Machinery in Vertebrate Visual Cycle: Hint from Jawless Vertebrates Poliakov, Eugenia; Gubin, Alexander N.; Stearn, Olivia PLoS ONE, Vol. 7, Issue 11 https://doi.org/10.1371/journal.pone.0049975	journal	November 2012
A lecithin: Retinol acyltransferase activity in human and rat liver MacDonald, Paul N.; Ong, David E. Biochemical and Biophysical Research Communications, Vol. 156, Issue 1 https://doi.org/10.1016/S0006-291X(88)80818-0	journal	October 1988
Multiple Mechanisms Linked to Platelet Activation Result in Lysophosphatidic Acid and Sphingosine 1-Phosphate Generation in Blood Sano, Takamitsu; Baker, Daniel; Virag, Tamas Journal of Biological Chemistry, Vol. 277, Issue 24 https://doi.org/10.1074/jbc.M201289200	journal	April 2002
Structural Basis for the Acyltransferase Activity of Lecithin:Retinol Acyltransferase-like Proteins Golczak, Marcin; Kiser, Philip D.; Sears, Avery E. Journal of Biological Chemistry, Vol. 287, Issue 28 https://doi.org/10.1074/jbc.m112.361550	journal	May 2012
MolProbity: all-atom contacts and structure validation for proteins and nucleic acids Davis, I. W.; Leaver-Fay, A.; Chen, V. B. Nucleic Acids Research, Vol. 35, Issue Web Server https://doi.org/10.1093/nar/gkm216	journal	May 2007
A helical lid converts a sulfotransferase to a dehydratase Pakhomova, Svetlana; Kobayashi, Mime; Buck, Jochen Nature Structural Biology, Vol. 8, Issue 5, p. 447-451 https://doi.org/10.1038/87617	journal	May 2001
AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiency Jaworski, Kathy; Ahmadian, Maryam; Duncan, Robin E. Nature Medicine, Vol. 15, Issue 2 https://doi.org/10.1038/nm.1904	journal	January 2009
Aliphatic and enantioselective amidases: from hydrolysis to acyl transfer activity Fournand, D.; Arnaud, A. Journal of Applied Microbiology, Vol. 91, Issue 3 https://doi.org/10.1046/j.1365-2672.2001.01378.x	journal	September 2001
Adipose-specific phospholipase as regulator of adiposity Wolf, George Nutrition Reviews, Vol. 67, Issue 9 https://doi.org/10.1111/j.1753-4887.2009.00227.x	journal	September 2009
Binding of a Truncated Form of Lecithin:Retinol Acyltransferase and Its N- and C-Terminal Peptides to Lipid Monolayers Bussières, Sylvain; Cantin, Line; Desbat, Bernard Langmuir, Vol. 28, Issue 7 https://doi.org/10.1021/la203896n	journal	February 2012
Evolution of the Genetic Machinery of the Visual Cycle: A Novelty of the Vertebrate Eye? Albalat, R. Molecular Biology and Evolution, Vol. 29, Issue 5 https://doi.org/10.1093/molbev/msr313	journal	December 2011
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
Mutation of key residues of RPE65 abolishes its enzymatic role as isomerohydrolase in the visual cycle Redmond, T. M.; Poliakov, E.; Yu, S. Proceedings of the National Academy of Sciences, Vol. 102, Issue 38 https://doi.org/10.1073/pnas.0504167102	journal	September 2005
Structure and Function of Lipases Derewenda, Zygmunt S. Lipoproteins, Apolipoproteins, and Lipases https://doi.org/10.1016/S0065-3233(08)60637-3	book	January 1994
Hydrolysis and transesterification of platelet-activating factor by lecithin-cholesterol acyltransferase. Liu, M.; Subbaiah, P. V. Proceedings of the National Academy of Sciences, Vol. 91, Issue 13 https://doi.org/10.1073/pnas.91.13.6035	journal	June 1994
Evolution and tinkering Jacob, F. Science, Vol. 196, Issue 4295 https://doi.org/10.1126/science.860134	journal	June 1977
Rpe65 Is the Retinoid Isomerase in Bovine Retinal Pigment Epithelium Jin, Minghao; Li, Songhua; Moghrabi, Walid N. Cell, Vol. 122, Issue 3 https://doi.org/10.1016/j.cell.2005.06.042	journal	August 2005
Catalytic promiscuity and the evolution of new enzymatic activities O'Brien, Patrick J.; Herschlag, Daniel Chemistry & Biology, Vol. 6, Issue 4 https://doi.org/10.1016/s1074-5521(99)80033-7	journal	April 1999
New players in the fatty acyl ethanolamide metabolism Rahman, Iffat Ara Sonia; Tsuboi, Kazuhito; Uyama, Toru Pharmacological Research, Vol. 86 https://doi.org/10.1016/j.phrs.2014.04.001	journal	August 2014
The phospholipase A ₁ activity of lysophospholipase A-I links platelet activation to LPA production during blood coagulation Bolen, Alyssa L.; Naren, Anjaparavanda P.; Yarlagadda, Sunitha Journal of Lipid Research, Vol. 52, Issue 5 https://doi.org/10.1194/jlr.M013326	journal	March 2011
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
Solution structure of the N-terminal catalytic domain of human H-REV107 - A novel circular permutated NlpC/P60 domain Ren, Xiaobai; Lin, Jian; Jin, Changwen FEBS Letters, Vol. 584, Issue 19 https://doi.org/10.1016/j.febslet.2010.09.015	journal	September 2010
Turning a hobby into a job: How duplicated genes find new functions Conant, Gavin C.; Wolfe, Kenneth H. Nature Reviews Genetics, Vol. 9, Issue 12 https://doi.org/10.1038/nrg2482	journal	December 2008
Lipid signalling in disease Wymann, Matthias P.; Schneiter, Roger Nature Reviews Molecular Cell Biology, Vol. 9, Issue 2 https://doi.org/10.1038/nrm2335	journal	February 2008
Characterization of the human tumor suppressors TIG3 and HRASLS2 as phospholipid-metabolizing enzymes Uyama, Toru; Jin, Xing-Hua; Tsuboi, Kazuhito Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Vol. 1791, Issue 12 https://doi.org/10.1016/j.bbalip.2009.07.001	journal	December 2009
Overview of the CCP4 suite and current developments. Winn, Martyn D.; Ballard, Charles C.; Cowtan, Kevin D. Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.52322	text	January 2011
An Acyl-covalent Enzyme Intermediate of Lecithin:Retinol Acyltransferase Golczak, Marcin; Palczewski, Krzysztof Journal of Biological Chemistry, Vol. 285, Issue 38 https://doi.org/10.1074/jbc.M110.152314	journal	July 2010
Principles of fluorescence spectroscopy Ricchelli, Fernanda Journal of Photochemistry and Photobiology B: Biology, Vol. 3, Issue 2 https://doi.org/10.1016/1011-1344(89)80070-3	journal	April 1989
Chemistry of the Retinoid (Visual) Cycle Kiser, Philip D.; Golczak, Marcin; Palczewski, Krzysztof Chemical Reviews, Vol. 114, Issue 1 https://doi.org/10.1021/cr400107q	journal	July 2013
Generation of N -Acylphosphatidylethanolamine by Members of the Phospholipase A/Acyltransferase (PLA/AT) Family Uyama, Toru; Ikematsu, Natsuki; Inoue, Manami Journal of Biological Chemistry, Vol. 287, Issue 38 https://doi.org/10.1074/jbc.M112.368712	journal	July 2012
Discovery and Characterization of a Ca2+-independent Phosphatidylethanolamine N-Acyltransferase Generating the Anandamide Precursor and Its Congeners Jin, X. -H.; Okamoto, Y.; Morishita, J. Journal of Biological Chemistry, Vol. 282, Issue 6 https://doi.org/10.1074/jbc.M606369200	journal	November 2006
Importance of Membrane Structural Integrity for RPE65 Retinoid Isomerization Activity Golczak, Marcin; Kiser, Philip D.; Lodowski, David T. Journal of Biological Chemistry, Vol. 285, Issue 13 https://doi.org/10.1074/jbc.M109.063941	journal	January 2010
Optimal description of a protein structure in terms of multiple groups undergoing TLS motion Painter, Jay; Merritt, Ethan A. Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 4 https://doi.org/10.1107/S0907444906005270	journal	March 2006
Lecithin-retinol Acyltransferase Is Essential for Accumulation of All- trans -Retinyl Esters in the Eye and in the Liver Batten, Matthew L.; Imanishi, Yoshikazu; Maeda, Tadao Journal of Biological Chemistry, Vol. 279, Issue 11 https://doi.org/10.1074/jbc.M312410200	journal	December 2003
Enzymes Without Borders: Mobilizing Substrates, Delivering Products Forneris, F.; Mattevi, A. Science, Vol. 321, Issue 5886 https://doi.org/10.1126/science.1151118	journal	July 2008
Lecithin Retinol Acyltransferase Forms Functional Homodimers Jahng, Wan Jin; Cheung, Eric; Rando, Robert R. Biochemistry, Vol. 41, Issue 23 https://doi.org/10.1021/bi025163+	journal	May 2002
Lecithin Retinol Acyltransferase Forms Functional Homodimers ^† Jahng, Wan Jin; Cheung, Eric; Rando, Robert R. Biochemistry, Vol. 41, Issue 20 https://doi.org/10.1021/bi015710b	journal	May 2002
Purification and Characterization of a Transmembrane Domain-Deleted Form of Lecithin Retinol Acyltransferase ^† Bok, Dean; Ruiz, Alberto; Yaron, Orna Biochemistry, Vol. 42, Issue 20 https://doi.org/10.1021/bi0342416	journal	May 2003
Metabolic Basis of Visual Cycle Inhibition by Retinoid and Nonretinoid Compounds in the Vertebrate Retina Golczak, Marcin; Maeda, Akiko; Bereta, Grzegorz Journal of Biological Chemistry, Vol. 283, Issue 15 https://doi.org/10.1074/jbc.M708982200	journal	January 2008
The tumor suppressor gene H-Rev107 functions as a novel Ca ²⁺ -independent cytosolic phospholipase A _1/2 of the thiol hydrolase type Uyama, Toru; Morishita, Jun; Jin, Xing-Hua Journal of Lipid Research, Vol. 50, Issue 4 https://doi.org/10.1194/jlr.M800453-JLR200	journal	December 2008
Enzyme Promiscuity: A Mechanistic and Evolutionary Perspective Khersonsky, Olga; Tawfik, Dan S. Annual Review of Biochemistry, Vol. 79, Issue 1, p. 471-505 https://doi.org/10.1146/annurev-biochem-030409-143718	journal	June 2010
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
Structure/Function Relationships of Adipose Phospholipase A ₂ Containing a Cys-His-His Catalytic Triad Pang, Xiao-Yan; Cao, Jian; Addington, Linsee Journal of Biological Chemistry, Vol. 287, Issue 42 https://doi.org/10.1074/jbc.M112.398859	journal	August 2012
Lecithin:Retinol Acyltransferase in Retinal Pigment Epithelial Microsomes Saari, J. C.; Bredberg, D. L. Journal of Biological Chemistry, Vol. 264, Issue 15 https://doi.org/10.1016/S0021-9258(18)81839-7	journal	May 1989

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59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
Biochemistry
Enzyme mechanisms
Membranes
X-ray crystallography
acyltransferase
LRAT
vitamin A
retinol
HRAS-like tumor suppressor

Title: LRAT-specific domain facilitates vitamin A metabolism by domain swapping in HRASLS3

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