Structural mechanism for cargo recognition by the retromer complex

• María Lucas ^[1] ; David C. Gershlick ^[2] ; Ander Vidaurrazaga ^[1]
  1. [1] Centro de Investigación Cooperativa en Biotecnología

     Centro de Investigación Cooperativa en Biotecnología

     Derio, España

     
  2. [2] National Institutes of Health

     National Institutes of Health

     Estados Unidos

     
• Localización: Cell, ISSN 0092-8674, Vol. 167, Nº. 6, 2016, págs. 1623-1635
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Retromer is a multi-protein complex that recycles transmembrane cargo from endosomes to the trans-Golgi network and the plasma membrane. Defects in retromer impair various cellular processes and underlie some forms of Alzheimer’s disease and Parkinson’s disease. Although retromer was discovered over 15 years ago, the mechanisms for cargo recognition and recruitment to endosomes have remained elusive. Here, we present an X-ray crystallographic analysis of a four-component complex comprising the VPS26 and VPS35 subunits of retromer, the sorting nexin SNX3, and a recycling signal from the divalent cation transporter DMT1-II. This analysis identifies a binding site for canonical recycling signals at the interface between VPS26 and SNX3. In addition, the structure highlights a network of cooperative interactions among the VPS subunits, SNX3, and cargo that couple signal-recognition to membrane recruitment.