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PX-domain of human sorting nexin-7 (SNX7)

PDB Code 3IQ2 Target Class Phosphoinosotide dependent signalling Target SNX7 Alias DKFZp564F052, MGC8717, SNX7 Disease Area/Function signalling Date Deposited Aug 19 2009 Authors T.KARLBERG, M.WISNIEWSKA, C.H.ARROWSMITH, H.BERGLUND, C.BOUNTRA, R.COLLINS, A.M.EDWARDS, S.FLODIN, A.FLORES, S.GRASLUND, M.HAMMARSTROM, A.JOHANSSON, I.JOHANSSON, A.KALLAS, T.KOTENYOVA, A.KOTZSCH, P.KRAULIS, T.K.NIELSEN, M.MOCHE, P.NORDLUND, T.NYMAN, C.PERSSON, A.K.ROOS, P.SCHUTZ, M.I.SIPONEN, A.G.THORSELL, L.TRESAUGUES, S.VAN DEN ERG, J.WEIGELT, M.WELIN, H.SCHULER, Structural Genomics Consortium (SGC)

About this structure

Sorting nexins (SNXs) are a family of membrane associated proteins characterized by the presence of a phox (PX) homology domain [reviewed in 1-3]. The PX-domain confers specificity towards phosphoinositides, and targets the SNX proteins to membrane domains enriched in specific phospholipids [4, 5]. Human sorting nexin-7 [6] belongs to a 12-member SNX-BAR subfamily; in addition to the N-terminal PX-domain, SNX7 features a C-terminal BAR-domain. The BAR-domain contributes to protein targeting vesicular membranes [7].

We have previously solved the PX-domain of human SNX17 (pdb: 3FOG). Here we present the crystal structure of the PX domain of human SNX7 at 1.7 Å resolution. The structure was solved by molecular replacement with the PX-domain structure of yeast snx3 (pdb: 1ocs) as a search model. The asymmetric unit consisted of two interlocked polypeptide chains. The overall fold is a β-sheet with three antiparallel β-strands and an adjacent helical subdomain consisting of three α-helices. Although the putative ligand inositide(1,3,4,5,6)pentaphosphate was present in crystallization the phospoinositide was not visible in the electron density. Coordinates and structure factors have been deposited in the PDB with accession code 3IQ2.

References

  1. Carlton J, Bujny M, Rutherford A and Cullen P. (2005) Sorting Nexins – Unifying Trends and New Perspectives. Traffic 6: 75-82.
  2. Cullen P. (2008) Endosomal sorting and signalling: an emerging role for sorting nexins. Nature Rev. 9: 574-582.
  3. Seet L-F. and Hong W. (2006) The phox (PX) domain proteins and membrane traffic. Biochim. Biophys. Acta 1761: 878-896.
  4. Kanai F, Liu H, Field SJ, Akbary H, Matsuo T, Brown GE, Cantley LC and Yaffe M.B. (2001) The PX domains of p47phox and p40phox bind to lipid products of PI(3)K. Nat Cell Biol. 3: 675–678.
  5. Cheever ML, Sato TK, de Beer T, Kutateladze TG, Emr SD and Overduin M (2001) Phox domain interaction with PtdIns(3)P targets the Vam7 t-SNARE to vacuole membranes. Nat Cell Biol. 3: 613–618.
  6. Teasdale RD, Loci D, Houghton F, Karlsson L and Gleeson PA (2001) A large family of endosome-localized proteins related to sorting nexin 1. Biochem J 358: 7-16
  7. McMahon HT and Gallop JL (2005) Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature 438: 590–596.