spacer
spacer

PDBsum entry 2r17

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Protein transport PDB id
2r17
Jmol
Contents
Protein chains
183 a.a. *
298 a.a. *
276 a.a. *
Ligands
GOL ×2
Waters ×49
* Residue conservation analysis
PDB id:
2r17
Name: Protein transport
Title: Functional architecture of the retromer cargo-recognition co
Structure: Vacuolar protein sorting-associated protein 29. Chain: a, b. Synonym: vesicle protein sorting 29, hvps29, pep11. Engineered: yes. Vacuolar protein sorting-associated protein 35. Chain: c, d. Synonym: vesicle protein sorting 35, hvps35, maternal-embry engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: vps29. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: vps35, mem3.
Resolution:
2.80Å     R-factor:   0.216     R-free:   0.268
Authors: A.Hierro,A.L.Rojas,R.Rojas,N.Murthy,G.Effantin,A.V.Kajava,A. J.S.Bonifacino,J.H.Hurley
Key ref:
A.Hierro et al. (2007). Functional architecture of the retromer cargo-recognition complex. Nature, 449, 1063-1067. PubMed id: 17891154 DOI: 10.1038/nature06216
Date:
22-Aug-07     Release date:   30-Oct-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9UBQ0  (VPS29_HUMAN) -  Vacuolar protein sorting-associated protein 29
Seq:
Struc:
182 a.a.
183 a.a.
Protein chain
Pfam   ArchSchema ?
Q96QK1  (VPS35_HUMAN) -  Vacuolar protein sorting-associated protein 35
Seq:
Struc:
 
Seq:
Struc:
796 a.a.
298 a.a.
Protein chain
Pfam   ArchSchema ?
Q96QK1  (VPS35_HUMAN) -  Vacuolar protein sorting-associated protein 35
Seq:
Struc:
 
Seq:
Struc:
796 a.a.
276 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   10 terms 
  Biological process     transport   5 terms 
  Biochemical function     protein binding     4 terms  

 

 
DOI no: 10.1038/nature06216 Nature 449:1063-1067 (2007)
PubMed id: 17891154  
 
 
Functional architecture of the retromer cargo-recognition complex.
A.Hierro, A.L.Rojas, R.Rojas, N.Murthy, G.Effantin, A.V.Kajava, A.C.Steven, J.S.Bonifacino, J.H.Hurley.
 
  ABSTRACT  
 
The retromer complex is required for the sorting of acid hydrolases to lysosomes, transcytosis of the polymeric immunoglobulin receptor, Wnt gradient formation, iron transporter recycling and processing of the amyloid precursor protein. Human retromer consists of two smaller complexes: the cargo recognition VPS26-VPS29-VPS35 heterotrimer and a membrane-targeting heterodimer or homodimer of SNX1 and/or SNX2 (ref. 13). Here we report the crystal structure of a VPS29-VPS35 subcomplex showing how the metallophosphoesterase-fold subunit VPS29 (refs 14, 15) acts as a scaffold for the carboxy-terminal half of VPS35. VPS35 forms a horseshoe-shaped, right-handed, alpha-helical solenoid, the concave face of which completely covers the metal-binding site of VPS29, whereas the convex face exposes a series of hydrophobic interhelical grooves. Electron microscopy shows that the intact VPS26-VPS29-VPS35 complex is a stick-shaped, flexible structure, approximately 21 nm long. A hybrid structural model derived from crystal structures, electron microscopy, interaction studies and bioinformatics shows that the alpha-solenoid fold extends the full length of VPS35, and that VPS26 is bound at the opposite end from VPS29. This extended structure presents multiple binding sites for the SNX complex and receptor cargo, and appears capable of flexing to conform to curved vesicular membranes.
 
  Selected figure(s)  
 
Figure 1.
Figure 1: Structure of the VPS29–VPS35 subcomplex. a, VPS29 is green and VPS35 red. b, The surface of VPS35 is shown, with the residues blocking the metallophosphoesterase site of VPS29 in grey, and other residues that contact VPS29 in purple. c, The surface of VPS29 is shown, with residues surrounding the metallophosphoesterase site in light blue, and other VPS35-contacting residues in purple. d, Hydrophobic grooves on the outer surface of VPS35 are formed between even-numbered helices. The probability of the surface to participate in ligand binding was coloured from lowest to highest in a blue to red gradient using the hotpatch server (http://hotpatch.mbi.ucla.edu/). Structural figures were generated with pymol (http://www.pymol.org/).
Figure 4.
Figure 4: Integration of cargo and targeting signals by the cargo-recognition complex. a, The VPS26–VPS29–VPS35 complex is predicted to align roughly parallel to the membrane (green line at bottom), such that its multiple SNX^4, ^15 and cargo-binding sites^25 cooperatively interact. The arrows mark the central region about which VPS35 is proposed to flex so as to interact with cargo embedded in curved membranes. Binding sites that have been mapped to individual residues within crystallized components are coloured dark blue. Binding sites that have been mapped to regions of VPS35 or to as yet non-crystallized portions of VPS35 are marked by red bars aligned with the region of interest. Binding sites for yeast cargo proteins are not necessarily conserved in human VPS35; however, the overall architecture of the yeast and other orthologous complexes is proposed to be very similar to the human complex. b, Schematic rendering of a speculative model for the retromer coat on a tubular vesicle, coloured as above, with the SNX dimer in purple.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2007, 449, 1063-1067) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22193161 P.J.Cullen, and H.C.Korswagen (2012).
Sorting nexins provide diversity for retromer-dependent trafficking events.
  Nat Cell Biol, 14, 29-37.  
20936498 E.Gharakhanian, O.Chima-Okereke, D.K.Olson, C.Frost, and M.Kathleen Takahashi (2011).
env1 Mutant of VPS35 gene exhibits unique protein localization and processing phenotype at Golgi and lysosomal vacuole in Saccharomyces cerevisiae.
  Mol Cell Biochem, 346, 187-195.  
20875039 S.J.Norwood, D.J.Shaw, N.P.Cowieson, D.J.Owen, R.D.Teasdale, and B.M.Collins (2011).
Assembly and solution structure of the core retromer protein complex.
  Traffic, 12, 56-71.
PDB codes: 3lh8 3lh9 3lha
21481773 T.L.Yeh, C.Y.Lee, L.M.Amzel, P.J.Espenshade, and M.A.Bianchet (2011).
The hypoxic regulator of sterol synthesis nro1 is a nuclear import adaptor.
  Structure, 19, 503-514.
PDB code: 3msv
21445058 T.N.Feinstein, V.L.Wehbi, J.A.Ardura, D.S.Wheeler, S.Ferrandon, T.J.Gardella, and J.P.Vilardaga (2011).
Retromer terminates the generation of cAMP by internalized PTH receptors.
  Nat Chem Biol, 7, 278-284.  
19796370 S.Niemes, M.Langhans, C.Viotti, D.Scheuring, M.San Wan Yan, L.Jiang, S.Hillmer, D.G.Robinson, and P.Pimpl (2010).
Retromer recycles vacuolar sorting receptors from the trans-Golgi network.
  Plant J, 61, 107-121.  
19783821 B.Loll, M.Gebhardt, E.Wahle, and A.Meinhart (2009).
Crystal structure of the EndoG/EndoGI complex: mechanism of EndoG inhibition.
  Nucleic Acids Res, 37, 7312-7320.
PDB code: 3ism
19361443 G.Effantin, R.Rosenzweig, M.H.Glickman, and A.C.Steven (2009).
Electron microscopic evidence in support of alpha-solenoid models of proteasomal subunits Rpn1 and Rpn2.
  J Mol Biol, 386, 1204-1211.  
18835459 J.B.Dacks, A.A.Peden, and M.C.Field (2009).
Evolution of specificity in the eukaryotic endomembrane system.
  Int J Biochem Cell Biol, 41, 330-340.  
19794886 L.Aubry, D.Guetta, and G.Klein (2009).
The arrestin fold: variations on a theme.
  Curr Genomics, 10, 133-142.  
19553671 L.M.Koharudin, W.Furey, H.Liu, Y.J.Liu, and A.M.Gronenborn (2009).
The phox domain of sorting nexin 5 lacks phosphatidylinositol 3-phosphate (PtdIns(3)P) specificity and preferentially binds to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2).
  J Biol Chem, 284, 23697-23707.  
19201590 M.C.Field, and J.B.Dacks (2009).
First and last ancestors: reconstructing evolution of the endomembrane system with ESCRTs, vesicle coat proteins, and nuclear pore complexes.
  Curr Opin Cell Biol, 21, 4.  
19531583 M.N.Seaman, M.E.Harbour, D.Tattersall, E.Read, and N.Bright (2009).
Membrane recruitment of the cargo-selective retromer subcomplex is catalysed by the small GTPase Rab7 and inhibited by the Rab-GAP TBC1D5.
  J Cell Sci, 122, 2371-2382.  
19801656 M.Podobnik, R.Tyagi, N.Matange, U.Dermol, A.K.Gupta, R.Mattoo, K.Seshadri, and S.S.Visweswariah (2009).
A mycobacterial cyclic AMP phosphodiesterase that moonlights as a modifier of cell wall permeability.
  J Biol Chem, 284, 32846-32857.
PDB codes: 3ib7 3ib8
19139087 N.Naslavsky, J.McKenzie, N.Altan-Bonnet, D.Sheff, and S.Caplan (2009).
EHD3 regulates early-endosome-to-Golgi transport and preserves Golgi morphology.
  J Cell Sci, 122, 389-400.  
19520852 P.Adams, E.Kandiah, G.Effantin, A.C.Steven, and E.Ehrenfeld (2009).
Poliovirus 2C protein forms homo-oligomeric structures required for ATPase activity.
  J Biol Chem, 284, 22012-22021.  
19874558 V.Popoff, G.A.Mardones, S.K.Bai, V.Chambon, D.Tenza, P.V.Burgos, A.Shi, P.Benaroch, S.Urbé, C.Lamaze, B.D.Grant, G.Raposo, and L.Johannes (2009).
Analysis of articulation between clathrin and retromer in retrograde sorting on early endosomes.
  Traffic, 10, 1868-1880.  
18088321 B.M.Collins, S.J.Norwood, M.C.Kerr, D.Mahony, M.N.Seaman, R.D.Teasdale, and D.J.Owen (2008).
Structure of Vps26B and Mapping of its Interaction with the Retromer Protein Complex.
  Traffic, 9, 366-379.
PDB code: 2r51
18541005 B.M.Collins (2008).
The structure and function of the retromer protein complex.
  Traffic, 9, 1811-1822.  
18472259 J.S.Bonifacino, and J.H.Hurley (2008).
Retromer.
  Curr Opin Cell Biol, 20, 427-436.  
18467557 K.Tarassov, V.Messier, C.R.Landry, S.Radinovic, M.M.Molina, I.Shames, Y.Malitskaya, J.Vogel, H.Bussey, and S.W.Michnick (2008).
An in vivo map of the yeast protein interactome.
  Science, 320, 1465-1470.  
19109890 L.Johannes, and V.Popoff (2008).
Tracing the retrograde route in protein trafficking.
  Cell, 135, 1175-1187.  
18627577 M.S.Otegui, and C.Spitzer (2008).
Endosomal functions in plants.
  Traffic, 9, 1589-1598.  
18502633 P.G.Woodman, and C.E.Futter (2008).
Multivesicular bodies: co-ordinated progression to maturity.
  Curr Opin Cell Biol, 20, 408-414.  
18523436 P.J.Cullen (2008).
Endosomal sorting and signalling: an emerging role for sorting nexins.
  Nat Rev Mol Cell Biol, 9, 574-582.  
18817523 P.J.McCormick, K.Dumaresq-Doiron, A.S.Pluviose, V.Pichette, G.Tosato, and S.Lefrancois (2008).
Palmitoylation controls recycling in lysosomal sorting and trafficking.
  Traffic, 9, 1984-1997.  
18981234 R.Rojas, T.van Vlijmen, G.A.Mardones, Y.Prabhu, A.L.Rojas, S.Mohammed, A.J.Heck, G.Raposo, P.van der Sluijs, and J.S.Bonifacino (2008).
Regulation of retromer recruitment to endosomes by sequential action of Rab5 and Rab7.
  J Cell Biol, 183, 513-526.  
18768754 T.I.Strochlic, B.C.Schmiedekamp, J.Lee, D.J.Katzmann, and C.G.Burd (2008).
Opposing activities of the Snx3-retromer complex and ESCRT proteins mediate regulated cargo sorting at a common endosome.
  Mol Biol Cell, 19, 4694-4706.  
  19825591 X.Gao, S.Nagawa, G.Wang, and Z.Yang (2008).
Cell polarity signaling: focus on polar auxin transport.
  Mol Plant, 1, 899-909.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.