PMID- 2007623
OWN - NLM
STAT- MEDLINE
DCOM- 19910430
LR  - 20191210
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 113
IP  - 1
DP  - 1991 Apr
TI  - Assembly and routing of von Willebrand factor variants: the requirements for 
      disulfide-linked dimerization reside within the carboxy-terminal 151 amino acids.
PG  - 195-205
AB  - The precursor protein of von Willebrand factor (pro-vWF) consists of four 
      different repeated domains, denoted D1-D2-D'-D3-A1-A2-A3-D4-B1-B2-B3-C1-C2, 
      followed by a carboxy-terminal region of 151 amino acids without obvious internal 
      homology. Previously, we have shown the requirement of the domains D1, D2, D', 
      and D3 of pro-vWF in the assembly of pro-vWF dimers into multimers. Here, we 
      define the domains of vWF involved in dimerization, using deletion mutants of 
      full-length vWF cDNA transiently expressed in monkey kidney COS-1 cells. It is 
      shown that only the carboxy-terminal 151 amino acid residues of vWF are required 
      for dimerization. In addition, by analyzing a construct, encoding only the 
      carboxy-terminal 151 amino acids of vWF, we find that the formation of dimers is 
      an event independent of other domains present on pro-vWF, such as the domains C1 
      and C2 previously suggested to be involved in dimerization. Furthermore, it is 
      shown that a deletion mutant of vWF, lacking the carboxy-terminal 151 amino acid 
      residues and thus unable to dimerize, is proteolytically degraded in the ER. In 
      contrast, a mutant protein, composed only of the carboxy-terminal 151 amino acids 
      of vWF, and able to dimerize, is transported from the ER in a similar fashion as 
      wild-type vWF. The role of the ER in the assembly of vWF is discussed with regard 
      to the data presented in this paper on the intracellular fate of several vWF 
      mutant proteins.
FAU - Voorberg, J
AU  - Voorberg J
AD  - Department of Molecular Biology, Central Laboratory of the Netherlands Red Cross 
      Blood Transfusion Service, Amsterdam.
FAU - Fontijn, R
AU  - Fontijn R
FAU - Calafat, J
AU  - Calafat J
FAU - Janssen, H
AU  - Janssen H
FAU - van Mourik, J A
AU  - van Mourik JA
FAU - Pannekoek, H
AU  - Pannekoek H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Disulfides)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Oligonucleotides)
RN  - 0 (Protein Precursors)
RN  - 0 (von Willebrand Factor)
RN  - EC 3.2.1.- (Hexosaminidases)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Biological Transport
MH  - Blotting, Western
MH  - Cell Line
MH  - Chlorocebus aethiops
MH  - Cloning, Molecular
MH  - DNA Mutational Analysis
MH  - Disulfides
MH  - Endoplasmic Reticulum/metabolism
MH  - Hexosaminidases/pharmacology
MH  - Immunohistochemistry
MH  - Lysosomes/metabolism
MH  - Macromolecular Substances
MH  - Microscopy, Electron
MH  - Molecular Sequence Data
MH  - Molecular Structure
MH  - Molecular Weight
MH  - Oligonucleotides/chemistry
MH  - Protein Precursors/metabolism
MH  - Structure-Activity Relationship
MH  - von Willebrand Factor/*chemistry/metabolism
PMC - PMC2288914
EDAT- 1991/04/01 00:00
MHDA- 1991/04/01 00:01
PMCR- 1991/10/01
CRDT- 1991/04/01 00:00
PHST- 1991/04/01 00:00 [pubmed]
PHST- 1991/04/01 00:01 [medline]
PHST- 1991/04/01 00:00 [entrez]
PHST- 1991/10/01 00:00 [pmc-release]
AID - 91177957 [pii]
AID - 10.1083/jcb.113.1.195 [doi]
PST - ppublish
SO  - J Cell Biol. 1991 Apr;113(1):195-205. doi: 10.1083/jcb.113.1.195.