en
Scientific article
English

Deletion of 3 residues from the C-terminus of MCFD2 affects binding to ERGIC-53 and causes combined factor V and factor VIII deficiency

Published inBlood, vol. 111, no. 3, p. 1299-1301
Publication date2008
Abstract

Combined factor V and factor VIII deficiency (F5F8D) is a rare, autosomal recessive coagulation disorder. F5F8D is genetically linked to mutations in the transmembrane lectin ERGIC-53 and its soluble interaction partner MCFD2. The ERGIC-53/MCFD2 protein complex functions as transport receptor of coagulation factors V and VIII by mediating their export from the endoplasmic reticulum (ER). Here, we studied a F5F8D patient who was found to be a compound heterozygote for 2 novel mutations in MCFD2: a large deletion of 8.4 kb eliminating the 5'UTR of the gene and a nonsense mutation resulting in the deletion of only 3 amino acids (DeltaSLQ) from the C-terminus of MCFD2. Biochemical and structural analysis of the DeltaSLQ mutant demonstrated impaired binding to ERGIC-53 due to modification of the 3-dimensional structure of MCFD2. Our results highlight the importance of the ERGIC-53/MCFD2 protein interaction for the efficient secretion of coagulation factors V and VIII.

Keywords
  • Amino Acid Sequence
  • Child
  • Factor V Deficiency/genetics/metabolism
  • Female
  • Gene Deletion
  • Hemophilia A/genetics/metabolism
  • Humans
  • Male
  • Mannose-Binding Lectins/metabolism
  • Membrane Proteins/metabolism
  • Molecular Sequence Data
  • Protein Binding
  • Vesicular Transport Proteins/chemistry/genetics/metabolism
Citation (ISO format)
NYFELER, Beat et al. Deletion of 3 residues from the C-terminus of MCFD2 affects binding to ERGIC-53 and causes combined factor V and factor VIII deficiency. In: Blood, 2008, vol. 111, n° 3, p. 1299–1301. doi: 10.1182/blood-2007-09-112854
Main files (1)
Article (Accepted version)
accessLevelRestricted
Identifiers
ISSN of the journal0006-4971
561views
0downloads

Technical informations

Creation05/28/2009 10:01:00 AM
First validation05/28/2009 10:01:00 AM
Update time03/14/2023 3:05:49 PM
Status update03/14/2023 3:05:49 PM
Last indexation01/15/2024 6:30:17 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack