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

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 coa...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Blood Jg. 111; H. 3; S. 1299
Hauptverfasser:	Nyfeler, Beat, Kamiya, Yukiko, Boehlen, Françoise, Yamamoto, Kazuo, Kato, Koichi, de Moerloose, Philippe, Hauri, Hans-Peter, Neerman-Arbez, Marguerite
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 01.02.2008
Schlagworte:	Amino Acid Sequence Child Factor V Deficiency - genetics Factor V Deficiency - metabolism Female Gene Deletion Hemophilia A - genetics Hemophilia A - metabolism Humans Male Mannose-Binding Lectins - metabolism Membrane Proteins - metabolism Molecular Sequence Data Protein Binding Vesicular Transport Proteins - chemistry Vesicular Transport Proteins - genetics Vesicular Transport Proteins - metabolism
ISSN:	0006-4971
Online-Zugang:	Weitere Angaben
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	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.
Bibliographie:	ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3
ISSN:	0006-4971
DOI:	10.1182/blood-2007-09-112854