Crystal structure of two CD46 domains reveals an extended measles virus-binding surface.

نویسندگان

  • J M Casasnovas
  • M Larvie
  • T Stehle
چکیده

Measles virus is a paramyxovirus which, like other members of the family such as respiratory syncytial virus, is a major cause of morbidity and mortality worldwide. The cell surface receptor for measles virus in humans is CD46, a complement cofactor. We report here the crystal structure at 3.1 A resolution of the measles virus-binding fragment of CD46. The structure reveals the architecture and spatial arrangement of two glycosylated short consensus repeats with a pronounced interdomain bend and some flexibility at the domain interface. Amino acids involved in measles virus binding define a large, glycan-free surface that extends from the top of the first to the bottom of the second repeat. The extended virus-binding surface of CD46 differs strikingly from those reported for the human virus receptor proteins CD4 and intercellular cell adhesion molecule-1 (ICAM-1), suggesting that the CD46 structure utilizes a novel mode of virus recognition. A highly hydrophobic and protruding loop at the base of the first repeat bears a critical virus-binding residue, thereby defining an important recognition epitope. Molecules that mimic the conformation of this loop potentially could be effective anti-viral agents by preventing binding of measles virus to CD46.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Diffraction Analysis of a CD46 4-Domain Crystal Form

No. larv8536 Beamline(s): X12C, X25 Introduction: CD46, also known as membrane cofactor protein, is the cellular receptor for measles virus. The protein ectodomain consists of four concatenated “short consensus repeats” or SCR domains. Measles virus binds to domains SCR1 and SCR2, the natural ligands of CD46 (complement proteins C3b and C4b) bind to domains SCR3 and SCR4. We have recently deter...

متن کامل

Structure of the Extracellular Portion of CD46 Provides Insights into Its Interactions with Complement Proteins and Pathogens

The human membrane cofactor protein (MCP, CD46) is a central component of the innate immune system. CD46 protects autologous cells from complement attack by binding to complement proteins C3b and C4b and serving as a cofactor for their cleavage. Recent data show that CD46 also plays a role in mediating acquired immune responses, and in triggering autophagy. In addition to these physiologic func...

متن کامل

A CD46CD[55-46] chimeric receptor, eight short consensus repeats long, acts as an inhibitor of both CD46 (MCP)- and CD150 (SLAM)-mediated cell-cell fusion induced by CD46-using measles virus.

According to their cellular receptor use, measles virus (MV) strains can be separated into two phenotypes, CD46-using and CD46-non-using. A long chimeric receptor, CD46CD[55-46], was generated from the CD46 backbone, encompassing the four short consensus repeat (SCR) domains of CD46 linked via a flexible glycine hinge to SCR1 and SCR2 of CD55, SCR3 and SCR4 of CD46 and the STP, transmembrane an...

متن کامل

Binding of measles virus to membrane cofactor protein (CD46): importance of disulfide bonds and N-glycans for the receptor function.

Two cellular proteins, membrane cofactor protein (MCP) and moesin, were reported recently to be functionally associated with the initiation of a measles virus infection. We have analyzed the interaction of measles virus with cell surface proteins, using an overlay binding assay with cellular proteins immobilized on nitrocellulose. Among surface-biotinylated proteins from a human rectal tumor ce...

متن کامل

Cell-to-cell contact via measles virus haemagglutinin-CD46 interaction triggers CD46 downregulation.

CD46 downregulation by measles virus (MV) occurs after expression of virus haemagglutinin (H) protein on the surface of the infected cell and is a consequence of CD46-H interaction on the cell membrane. To assess whether CD46 downregulation also occurs after CD46-H interaction when these two molecules are expressed on distinct cells, we used human T cell line Jurkat (expressing CD46) and transf...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The EMBO journal

دوره 18 11  شماره 

صفحات  -

تاریخ انتشار 1999