5F0M

Structure of retromer VPS26-VPS35 subunits bound to SNX3 and DMT1 (SeMet labeled)

Summary for 5F0M

• Entry DOI: 10.2210/pdb5f0m/pdb
• Related: 2FAU 2R17 5F0J 5F0K 5F0L
• Descriptor: Vacuolar protein sorting-associated protein 35, Vacuolar protein sorting-associated protein 26A, Sorting nexin-3, ... (7 entities in total)
• Functional Keywords: protein transport, retromer, sorting nexin
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm: Q96QK1 O75436; Early endosome : O60493; Isoform 2: Cell membrane ; Multi- pass membrane protein . Endosome membrane ; Multi-pass membrane protein : P49281
• Total number of polymer chains: 4
• Total formula weight: 114395.37

Authors

Lucas, M.,Gershlick, D.,Vidaurrazaga, A.,Rojas, A.L.,Bonifacino, J.S.,Hierro, A. (deposition date: 2015-11-27, release date: 2016-12-07, Last modification date: 2024-10-16)

Primary citation

Lucas, M.,Gershlick, D.C.,Vidaurrazaga, A.,Rojas, A.L.,Bonifacino, J.S.,Hierro, A.
Structural Mechanism for Cargo Recognition by the Retromer Complex.
Cell, 167:1623-1635.e14, 2016

PubMed Abstract: 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.

PubMed: 27889239
DOI: 10.1016/j.cell.2016.10.056

Experimental method

X-RAY DIFFRACTION (3.1 Å)