PMID- 31949249
OWN - NLM
STAT- MEDLINE
DCOM- 20201110
LR  - 20210115
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 10
IP  - 1
DP  - 2020 Jan 16
TI  - The novel missense mutation Met48Lys in FKBP22 changes its structure and 
      functions.
PG  - 497
LID - 10.1038/s41598-019-57374-y [doi]
LID - 497
AB  - Mutations in the FKBP14 gene encoding FKBP22 (FK506 Binding Protein 22 kDa) cause 
      kyphoscoliotic Ehlers-Danlos Syndrome (kEDS). The first clinical report showed 
      that a lack of FKBP22 protein due to mutations causing nonsense-mediated decay of 
      the mRNA leads to a wide spectrum of clinical phenotypes including progressive 
      kyphoscoliosis, joint hypermobility, hypotonia, hyperelastic skin, hearing loss 
      and aortic rupture. Our previous work showed that these phenotypic features could 
      be correlated with the functions of FKBP22, which preferentially binds to type 
      III, VI and X collagens, but not to type I, II or V collagens. We also showed 
      that FKBP22 catalyzed the folding of type III collagen through its prolyl 
      isomerase activity and acted as a molecular chaperone for type III collagen. 
      Recently, a novel missense mutation Met48Lys in FKBP22 was identified in a 
      patient with kEDS. In this report, we expand the list of substrates of FKBP22 and 
      also demonstrate that the Met48Lys mutation diminishes the activities of FKBP22, 
      indicating that pathology can arise from absence of FKBP22, or partial loss of 
      its function.
FAU - Ishikawa, Yoshihiro
AU  - Ishikawa Y
AUID- ORCID: 0000-0003-2013-0518
AD  - Department of Biochemistry and Molecular Biology, Oregon Health & Science 
      University, Portland, OR, USA. yoshi.molecularensemble@gmail.com.
AD  - Shriners Hospital for Children, Research Department, Portland, OR, USA. 
      yoshi.molecularensemble@gmail.com.
AD  - Department of Ophthalmology, University of California, School of Medicine, San 
      Francisco, CA, USA. yoshi.molecularensemble@gmail.com.
FAU - Mizuno, Nobuyo
AU  - Mizuno N
AD  - Shriners Hospital for Children, Research Department, Portland, OR, USA.
AD  - Vaccine and Gene Therapy Institute, Oregon Health and Science University, 
      Portland, Oregon, USA.
FAU - Holden, Paul
AU  - Holden P
AD  - Shriners Hospital for Children, Research Department, Portland, OR, USA.
FAU - Lim, Pei Jin
AU  - Lim PJ
AD  - Connective Tissue Unit, Division of Metabolism and Children's Research Centre, 
      University Children's Hospital, Zurich, Switzerland.
FAU - Gould, Douglas B
AU  - Gould DB
AD  - Department of Ophthalmology, University of California, School of Medicine, San 
      Francisco, CA, USA.
AD  - Department of Anatomy, University of California, School of Medicine, San 
      Francisco, CA, USA.
FAU - Rohrbach, Marianne
AU  - Rohrbach M
AD  - Connective Tissue Unit, Division of Metabolism and Children's Research Centre, 
      University Children's Hospital, Zurich, Switzerland.
FAU - Giunta, Cecilia
AU  - Giunta C
AD  - Connective Tissue Unit, Division of Metabolism and Children's Research Centre, 
      University Children's Hospital, Zurich, Switzerland.
FAU - Bachinger, Hans Peter
AU  - Bachinger HP
AD  - Department of Biochemistry and Molecular Biology, Oregon Health & Science 
      University, Portland, OR, USA.
LA  - eng
GR  - R01 NS096173/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200116
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Collagen Type III)
RN  - EC 5.2.1.8 (FKBP14 protein, human)
RN  - EC 5.2.1.8 (Peptidylprolyl Isomerase)
SB  - IM
MH  - Cells, Cultured
MH  - Circular Dichroism
MH  - Collagen Type III/chemistry/*metabolism
MH  - Humans
MH  - Models, Molecular
MH  - *Mutation, Missense
MH  - Peptidylprolyl Isomerase/*chemistry/genetics/*metabolism
MH  - Protein Conformation
MH  - Protein Folding
PMC - PMC6965642
COIS- The authors declare no competing interests.
EDAT- 2020/01/18 06:00
MHDA- 2020/11/11 06:00
PMCR- 2020/01/16
CRDT- 2020/01/18 06:00
PHST- 2019/06/17 00:00 [received]
PHST- 2019/12/28 00:00 [accepted]
PHST- 2020/01/18 06:00 [entrez]
PHST- 2020/01/18 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
PHST- 2020/01/16 00:00 [pmc-release]
AID - 10.1038/s41598-019-57374-y [pii]
AID - 57374 [pii]
AID - 10.1038/s41598-019-57374-y [doi]
PST - epublish
SO  - Sci Rep. 2020 Jan 16;10(1):497. doi: 10.1038/s41598-019-57374-y.