PMID- 11415439
OWN - NLM
STAT- MEDLINE
DCOM- 20010816
LR  - 20190501
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 357
IP  - Pt 1
DP  - 2001 Jul 1
TI  - Functional roles and efficiencies of the thioredoxin boxes of calcium-binding 
      proteins 1 and 2 in protein folding.
PG  - 83-95
AB  - The rat luminal endoplasmic-recticulum calcium-binding proteins 1 and 2 (CaBP1 
      and CaBP2 respectively) are members of the protein disulphide-isomerase (PDI) 
      family. They contain two and three thioredoxin boxes (Cys-Gly-His-Cys) 
      respectively and, like PDI, may be involved in the folding of nascent proteins. 
      We demonstrate here that CaBP1, similar to PDI and CaBP2, can complement the 
      lethal phenotype of the disrupted Saccharomyces cerevisiae PDI gene, provided 
      that the natural C-terminal Lys-Asp-Glu-Leu sequence is replaced by 
      His-Asp-Glu-Leu. Both the in vitro RNase AIII-re-activation assays and in vivo 
      pro-(carboxypeptidase Y) processing assays using CaBP1 and CaBP2 thioredoxin 
      (trx)-box mutants revealed that, whereas the three trx boxes in CaBP2 seem to be 
      functionally equivalent, the first trx box of CaBP1 is significantly more active 
      than the second trx box. Furthermore, only about 65% re-activation of denatured 
      reduced RNase AIII could be obtained with CaBP1 or CaBP2 compared with PDI, and 
      the yield of PDI-catalysed reactions was significantly reduced in the presence of 
      either CaBP1 or CaBP2. In contrast with PDI, neither CaBP1 nor CaBP2 could 
      catalyse the renaturation of denatured glyceraldehyde-3-phosphate dehydrogenase 
      (GAPDH), which is a redox-independent process, and neither protein had any effect 
      on the PDI-catalysed refolding of GAPDH. Furthermore, although PDI can bind 
      peptides via its b' domain, a property it shares with PDIp, the pancreas-specific 
      PDI homologue, and although PDI can bind malfolded proteins such as 'scrambled' 
      ribonuclease, no such interactions could be detected for CaBP2. We conclude that: 
      (1) both CaBP2 and CaBP1 lack peptide-binding activity for GAPDH attributed to 
      the C-terminal region of the a' domain of PDI; (2) CaBP2 lacks the general 
      peptide-binding activity attributed to the b' domain of PDI; (3) interaction of 
      CaBP2 with substrate (RNase AIII) is different from that of PDI and substrate; 
      and (4) both CaBP2 and CaBP1 may promote oxidative folding by different kinetic 
      pathways.
FAU - Kramer, B
AU  - Kramer B
AD  - Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Am 
      Fassberg 11, D37077 Gottingen, Germany.
FAU - Ferrari, D M
AU  - Ferrari DM
FAU - Klappa, P
AU  - Klappa P
FAU - Pohlmann, N
AU  - Pohlmann N
FAU - Soling, H D
AU  - Soling HD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Calcium-Binding Proteins)
RN  - 52500-60-4 (Thioredoxins)
RN  - EC 3.1.- (Ribonucleases)
RN  - EC 3.1.- (ribonuclease AIII)
RN  - EC 3.4.- (Carboxypeptidases)
RN  - EC 3.4.16.5 (Cathepsin A)
RN  - EC 5.3.4.- (Ca-binding protein 2)
RN  - EC 5.3.4.- (Ca2+-binding protein-1)
RN  - EC 5.3.4.- (Sulfur-Sulfur Bond Isomerases)
RN  - EC 5.3.4.1 (Protein Disulfide-Isomerases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Animals
MH  - Calcium-Binding Proteins/*chemistry/genetics/*metabolism
MH  - Carboxypeptidases/chemistry/metabolism
MH  - Cathepsin A
MH  - Endoplasmic Reticulum/metabolism
MH  - Kinetics
MH  - Mutagenesis, Site-Directed
MH  - Plasmids
MH  - Promoter Regions, Genetic
MH  - Protein Denaturation
MH  - Protein Disulfide-Isomerases/genetics/metabolism
MH  - *Protein Folding
MH  - Rats
MH  - Ribonucleases/chemistry/metabolism
MH  - Saccharomyces cerevisiae/*enzymology/genetics
MH  - Sulfur-Sulfur Bond Isomerases/*chemistry/genetics/*metabolism
MH  - Thioredoxins/*chemistry/metabolism
PMC - PMC1221931
EDAT- 2001/06/21 10:00
MHDA- 2001/08/17 10:01
PMCR- 2002/01/01
CRDT- 2001/06/21 10:00
PHST- 2001/06/21 10:00 [pubmed]
PHST- 2001/08/17 10:01 [medline]
PHST- 2001/06/21 10:00 [entrez]
PHST- 2002/01/01 00:00 [pmc-release]
AID - 10.1042/0264-6021:3570083 [doi]
PST - ppublish
SO  - Biochem J. 2001 Jul 1;357(Pt 1):83-95. doi: 10.1042/0264-6021:3570083.