PMID- 10562302
OWN - NLM
STAT- MEDLINE
DCOM- 19991209
LR  - 20220316
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 104
IP  - 10
DP  - 1999 Nov
TI  - Mutation causing congenital myasthenia reveals acetylcholine receptor beta/delta 
      subunit interaction essential for assembly.
PG  - 1403-10
AB  - We describe a severe postsynaptic congenital myasthenic syndrome with marked
      endplate acetylcholine receptor (AChR) deficiency caused by 2 heteroallelic
      mutations in the beta subunit gene. One mutation causes skipping of exon 8,
      truncating the beta subunit before its M1 transmembrane domain, and abolishing
      surface expression of pentameric AChR. The other mutation, a 3-codon deletion
      (beta426delEQE) in the long cytoplasmic loop between the M3 and M4 domains,
      curtails but does not abolish expression. By coexpressing beta426delEQE with
      combinations of wild-type subunits in 293 HEK cells, we demonstrate that
      beta426delEQE impairs AChR assembly by disrupting a specific interaction between 
      beta and delta subunits. Studies with related deletion and missense mutants
      indicate that secondary structure in this region of the beta subunit is crucial
      for interaction with the delta subunit. The findings imply that the mutated
      residues are positioned at the interface between beta and delta subunits and
      demonstrate contribution of this local region of the long cytoplasmic loop to
      AChR assembly.
FAU - Quiram, P A
AU  - Quiram PA
AD  - Receptor Biology Laboratory, Department of Physiology and Biophysics, Mayo
      Clinic, Rochester, Minnesota 55905, USA.
FAU - Ohno, K
AU  - Ohno K
FAU - Milone, M
AU  - Milone M
FAU - Patterson, M C
AU  - Patterson MC
FAU - Pruitt, N J
AU  - Pruitt NJ
FAU - Brengman, J M
AU  - Brengman JM
FAU - Sine, S M
AU  - Sine SM
FAU - Engel, A G
AU  - Engel AG
LA  - eng
GR  - R01 NS031744/NS/NINDS NIH HHS/United States
GR  - NS31744/NS/NINDS NIH HHS/United States
GR  - NS6277/NS/NINDS NIH HHS/United States
GR  - R37 NS031744/NS/NINDS NIH HHS/United States
GR  - R01 NS006277/NS/NINDS NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Codon)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Receptors, Cholinergic)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
SB  - IM
MH  - Acetylcholinesterase/metabolism
MH  - Alleles
MH  - Amino Acid Sequence
MH  - Animals
MH  - Child
MH  - Codon
MH  - Exons
MH  - Female
MH  - Humans
MH  - Macromolecular Substances
MH  - Male
MH  - Molecular Sequence Data
MH  - Motor Endplate/pathology/physiology
MH  - Muscle, Skeletal/*metabolism/pathology/physiopathology
MH  - Myasthenia Gravis, Neonatal/*genetics/pathology/physiopathology
MH  - Nuclear Family
MH  - Pedigree
MH  - Protein Structure, Secondary
MH  - Receptors, Cholinergic/chemistry/*genetics/metabolism
MH  - Reference Values
MH  - Sequence Alignment
MH  - *Sequence Deletion
MH  - Sequence Homology, Amino Acid
PMC - PMC409847
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - 10.1172/JCI8179 [doi]
PST - ppublish
SO  - J Clin Invest. 1999 Nov;104(10):1403-10. doi: 10.1172/JCI8179.