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Title: Visualization of a radical B12 enzyme with its G-protein chaperone

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2];  [1];  [2];  [3]
  1. Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Chemistry
  2. Univ. of Michigan, Ann Arbor, MI (United States). Dept. of Biological Chemistry
  3. Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Chemistry. Dept. of Biology. Howard Hughes Medical Inst.
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G-protein metallochaperones ensure fidelity during cofactor assembly for a variety of metalloproteins, including adenosylcobalamin (AdoCbl)-dependent methylmalonyl-CoA mutase and hydrogenase, and thus have both medical and biofuel development applications. In this paper, we present crystal structures of IcmF, a natural fusion protein of AdoCbl-dependent isobutyryl-CoA mutase and its corresponding G-protein chaperone, which reveal the molecular architecture of a G-protein metallochaperone in complex with its target protein. These structures show that conserved G-protein elements become ordered upon target protein association, creating the molecular pathways that both sense and report on the cofactor loading state. Structures determined of both apo- and holo-forms of IcmF depict both open and closed enzyme states, in which the cofactor-binding domain is alternatively positioned for cofactor loading and for catalysis. Finally and notably, the G protein moves as a unit with the cofactor-binding domain, providing a visualization of how a chaperone assists in the sequestering of a precious cofactor inside an enzyme active site.

Research Organization:
Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Univ. of Michigan, Ann Arbor, MI (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health (NIH) (United States)
Grant/Contract Number:
AC02-06CH11357; AC02-05CH11231; GM069857; DK45776; P41 GM103403
OSTI ID:
1171849
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, Issue 8; ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)Copyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 20 works
Citation information provided by
Web of Science

References (46)

Autoinhibition and Signaling by the Switch II Motif in the G-protein Chaperone of a Radical B 12 Enzyme journal August 2013
The subunit structure of methylmalonyl-CoA mutase from Propionibacterium shermanii journal June 1986
Novel B 12 -Dependent Acyl-CoA Mutases and Their Biotechnological Potential journal July 2012
Cobalamin-dependent dehydratases and a deaminase: Radical catalysis and reactivating chaperones journal February 2014
Multiple roles of ATP:cob(I)alamin adenosyltransferases in the conversion of B12 to coenzyme B12 journal July 2010
Assembly and Protection of the Radical Enzyme, Methylmalonyl-CoA Mutase, by Its Chaperone † journal August 2006
A G-protein editor gates coenzyme B12 loading and is corrupted in methylmalonic aciduria journal December 2009
Structure of UreG/UreF/UreH Complex Reveals How Urease Accessory Proteins Facilitate Maturation of Helicobacter pylori Urease journal October 2013
Objective comparison of protein structures: error-scaled difference distance matrices journal June 2000
Crystal Structure of Substrate Complexes of Methylmalonyl-CoA Mutase journal June 1999
A switch III motif relays signaling between a B12 enzyme and its G-protein chaperone journal July 2013
Radical Carbon Skeleton Rearrangements:  Catalysis by Coenzyme B 12 -Dependent Mutases journal June 2003
IcmF Is a Fusion between the Radical B 12 Enzyme Isobutyryl-CoA Mutase and Its G-protein Chaperone journal October 2009
Structures of the Human GTPase MMAA and Vitamin B 12 -dependent Methylmalonyl-CoA Mutase and Insight into Their Complex Formation journal September 2010
Features and development of Coot journal March 2010
Genetic disorders of vitamin B 12 metabolism: eight complementation groups – eight genes journal January 2010
GTP Hydrolysis by HypB is Essential for Nickel Insertion into Hydrogenases of Escherichia Coli journal May 1995
Cobalamin Coenzymes in Enzymology book March 2010
Conformational changes on substrate binding to methylmalonyl CoA mutase and new insights into the free radical mechanism journal June 1998
The product of the hypB gene, which is required for nickel incorporation into hydrogenases, is a novel guanine nucleotide-binding protein. journal February 1993
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
Crystal Structure and Mutagenesis of the Metallochaperone MeaB journal August 2007
Glutamate mutase from Clostridium cochlearium: the structure of a coenzyme B12-dependent enzyme provides new mechanistic insights journal August 1999
How coenzyme B12 radicals are generated: the crystal structure of methylmalonyl-coenzyme A mutase at 2 å resolution journal March 1996
Transition Metal Speciation in the Cell: Insights from the Chemistry of Metal Ion Receptors journal May 2003
Novel Coenzyme B 12 -dependent Interconversion of Isovaleryl-CoA and Pivalyl-CoA journal December 2011
GTP-dependent activation of urease apoprotein in complex with the UreD, UreF, and UreG accessory proteins journal September 1999
Structural Insights into HypB, a GTP-binding Protein That Regulates Metal Binding journal June 2006
Classification and evolution of P-loop GTPases and related ATPases journal March 2002
Mechanisms of coenzyme B12-dependent rearrangements journal February 1985
Copper Metallochaperones journal June 2010
Cloning of full-length methylmalonyl-CoA mutase from a cDNA library using the polymerase chain reaction journal February 1989
Protection and reactivation of human methylmalonyl-CoA mutase by MMAA protein journal January 2011
Nonlinear partial differential equations and applications: Identification of the gene responsible for the cblA complementation group of vitamin B12-responsive methylmalonic acidemia based on analysis of prokaryotic gene arrangements journal November 2002
Adenosyltransferase tailors and delivers coenzyme B12 journal February 2008
Understanding How Cells Allocate Metals Using Metal Sensors and Metallochaperones journal October 2005
A locking mechanism preventing radical damage in the absence of substrate, as revealed by the x-ray structure of lysine 5,6-aminomutase journal October 2004
It takes two to tango: regulation of G proteins by dimerization journal May 2009
Klebsiella aerogenes urease gene cluster: sequence of ureD and demonstration that four accessory genes (ureD, ureE, ureF, and ureG) are involved in nickel metallocenter biosynthesis. journal July 1992
Radical Use of Rossmann and TIM Barrel Architectures for Controlling Coenzyme B 12 Chemistry journal June 2012
X-Ray Diffraction data from Isobutyryl-coenzyme A mutase fused with bound adenosylcobalamin, GDP, and Mg (holo-IcmF/GDP), source of 4XC6 structure dataset May 2015
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome journal December 2019
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation journal February 2021
Radical Carbon Skeleton Rearrangements: Catalysis by Coenzyme B12-Dependent Mutases journal August 2003
Understanding How Cells Allocate Metals Using Metal Sensors and Metallochaperones journal January 2006
PHENIX: a comprehensive Python-based system for macromolecular structure solution. text January 2010

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
metallocofactor delivery
vitamin B12
metallochaperone
G protein
crystallography