Work

Crystal structure of the LMAN1‐CRD/MCFD2 transport receptor complex provides insight into combined deficiency of factor V and factor VIII

Year: 2010

Type: article

Abstract: LMAN1 is a glycoprotein receptor, mediating transfer from the ER to the ER-Golgi intermediate compartment. Together with the co-receptor MCFD2, it transports coagulation factors V and VIII. Mutations in LMAN1 and MCFD2 can cause combined deficiency of factors V and VIII (F5F8D). We present the crystal structure of the LMAN1/MCFD2 complex and relate it to patient mutations. Circular dichroism data show that the majority of the substitution mutations give rise to a disordered or severely destabilized MCFD2 protein. The few stable mutation variants are found in the binding surface of the complex leading to impaired LMAN1 binding and F5F8D.

Source: FEBS Letters

DOI: 10.1016/j.febslet.2010.02.009

Authors: Edvard Wigren, Jean-Marie Bourhis, Inari Kursula, Jodie E. Guy, Ylva Lindqvist

Institution: Karolinska Institutet

Language: English

Topic: Hemophilia Treatment and Research

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: European Commission, Vetenskapsrådet