PMID- 32092071
OWN - NLM
STAT- MEDLINE
DCOM- 20200514
LR  - 20240423
IS  - 1545-7885 (Electronic)
IS  - 1544-9173 (Print)
IS  - 1544-9173 (Linking)
VI  - 18
IP  - 2
DP  - 2020 Feb
TI  - Functional interactions between posttranslationally modified amino acids of 
      methyl-coenzyme M reductase in Methanosarcina acetivorans.
PG  - e3000507
LID - 10.1371/journal.pbio.3000507 [doi]
LID - e3000507
AB  - The enzyme methyl-coenzyme M reductase (MCR) plays an important role in mediating 
      global levels of methane by catalyzing a reversible reaction that leads to the 
      production or consumption of this potent greenhouse gas in methanogenic and 
      methanotrophic archaea. In methanogenic archaea, the alpha subunit of MCR (McrA) 
      typically contains four to six posttranslationally modified amino acids near the 
      active site. Recent studies have identified enzymes performing two of these 
      modifications (thioglycine and 5-[S]-methylarginine), yet little is known about 
      the formation and function of the remaining posttranslationally modified 
      residues. Here, we provide in vivo evidence that a dedicated 
      S-adenosylmethionine-dependent methyltransferase encoded by a gene we designated 
      methylcysteine modification (mcmA) is responsible for formation of 
      S-methylcysteine in Methanosarcina acetivorans McrA. Phenotypic analysis of 
      mutants incapable of cysteine methylation suggests that the S-methylcysteine 
      residue might play a role in adaption to mesophilic conditions. To examine the 
      interactions between the S-methylcysteine residue and the previously 
      characterized thioglycine, 5-(S)-methylarginine modifications, we generated M. 
      acetivorans mutants lacking the three known modification genes in all possible 
      combinations. Phenotypic analyses revealed complex, physiologically relevant 
      interactions between the modified residues, which alter the thermal stability of 
      MCR in a combinatorial fashion that is not readily predictable from the 
      phenotypes of single mutants. High-resolution crystal structures of inactive MCR 
      lacking the modified amino acids were indistinguishable from the fully modified 
      enzyme, suggesting that interactions between the posttranslationally modified 
      residues do not exert a major influence on the static structure of the enzyme but 
      rather serve to fine-tune the activity and efficiency of MCR.
FAU - Nayak, Dipti D
AU  - Nayak DD
AD  - Carl R. Woese Institute of Genomic Biology, University of Illinois, Urbana, 
      Illinois, United States of America.
AD  - Department of Microbiology, University of Illinois, Urbana, Illinois, United 
      States of America.
FAU - Liu, Andi
AU  - Liu A
AUID- ORCID: 0000-0002-8795-9614
AD  - Department of Microbiology, University of Illinois, Urbana, Illinois, United 
      States of America.
FAU - Agrawal, Neha
AU  - Agrawal N
AUID- ORCID: 0000-0002-0351-8791
AD  - Department of Biochemistry, University of Illinois, Urbana, Illinois, United 
      States of America.
FAU - Rodriguez-Carerro, Roy
AU  - Rodriguez-Carerro R
AUID- ORCID: 0000-0001-8447-5641
AD  - Department of Microbiology, University of Illinois, Urbana, Illinois, United 
      States of America.
FAU - Dong, Shi-Hui
AU  - Dong SH
AD  - Department of Biochemistry, University of Illinois, Urbana, Illinois, United 
      States of America.
FAU - Mitchell, Douglas A
AU  - Mitchell DA
AUID- ORCID: 0000-0002-9564-0953
AD  - Carl R. Woese Institute of Genomic Biology, University of Illinois, Urbana, 
      Illinois, United States of America.
AD  - Department of Microbiology, University of Illinois, Urbana, Illinois, United 
      States of America.
AD  - Department of Chemistry, University of Illinois, Urbana, Illinois, United States 
      of America.
FAU - Nair, Satish K
AU  - Nair SK
AD  - Department of Biochemistry, University of Illinois, Urbana, Illinois, United 
      States of America.
AD  - Center for Biophysics & Quantitative Biology, University of Illinois, Urbana, 
      Illinois, United States of America.
FAU - Metcalf, William W
AU  - Metcalf WW
AUID- ORCID: 0000-0002-0182-0671
AD  - Carl R. Woese Institute of Genomic Biology, University of Illinois, Urbana, 
      Illinois, United States of America.
AD  - Department of Microbiology, University of Illinois, Urbana, Illinois, United 
      States of America.
LA  - eng
GR  - R01 GM097142/GM/NIGMS NIH HHS/United States
GR  - S10 RR027109/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20200224
PL  - United States
TA  - PLoS Biol
JT  - PLoS biology
JID - 101183755
RN  - 0 (Amino Acids)
RN  - 0 (Archaeal Proteins)
RN  - 0 (Protein Subunits)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - EC 2.8.4.1 (methyl coenzyme M reductase)
SB  - IM
MH  - Amino Acids/*metabolism
MH  - Archaeal Proteins/genetics/metabolism
MH  - Catalytic Domain
MH  - Methanosarcina/*enzymology/genetics/growth & development/metabolism
MH  - Methylation
MH  - Methyltransferases/genetics/metabolism
MH  - Models, Molecular
MH  - Mutation
MH  - Operon
MH  - Oxidoreductases/*chemistry/genetics/*metabolism
MH  - Phenotype
MH  - Protein Processing, Post-Translational/genetics
MH  - Protein Subunits
MH  - Temperature
PMC - PMC7058361
COIS- The authors have declared that no competing interests exist.
EDAT- 2020/02/25 06:00
MHDA- 2020/05/15 06:00
PMCR- 2020/02/24
CRDT- 2020/02/25 06:00
PHST- 2019/09/04 00:00 [received]
PHST- 2020/02/04 00:00 [accepted]
PHST- 2020/03/05 00:00 [revised]
PHST- 2020/02/25 06:00 [pubmed]
PHST- 2020/05/15 06:00 [medline]
PHST- 2020/02/25 06:00 [entrez]
PHST- 2020/02/24 00:00 [pmc-release]
AID - PBIOLOGY-D-19-02599 [pii]
AID - 10.1371/journal.pbio.3000507 [doi]
PST - epublish
SO  - PLoS Biol. 2020 Feb 24;18(2):e3000507. doi: 10.1371/journal.pbio.3000507. 
      eCollection 2020 Feb.