PDBsum entry 1hxr

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protein metals Protein-protein interface(s) links
Metal binding protein PDB id
Protein chains
107 a.a. *
115 a.a. *
_ZN ×2
Waters ×187
* Residue conservation analysis
PDB id:
Name: Metal binding protein
Title: Crystal structure of mss4 at 1.65 angstroms
Structure: Guanine nucleotide exchange factor mss4. Chain: a, b. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
1.65Å     R-factor:   0.214     R-free:   0.256
Authors: Z.Zhu,J.J.Dumas,S.E.Lietzke,D.G.Lambright
Key ref:
Z.Zhu et al. (2001). A helical turn motif in Mss4 is a critical determinant of Rab binding and nucleotide release. Biochemistry, 40, 3027-3036. PubMed id: 11258916 DOI: 10.1021/bi002680o
16-Jan-01     Release date:   14-Feb-01    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q08326  (MSS4_RAT) -  Guanine nucleotide exchange factor MSS4
123 a.a.
107 a.a.
Protein chain
Pfam   ArchSchema ?
Q08326  (MSS4_RAT) -  Guanine nucleotide exchange factor MSS4
123 a.a.
115 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     transport   4 terms 
  Biochemical function     guanyl-nucleotide exchange factor activity     2 terms  


DOI no: 10.1021/bi002680o Biochemistry 40:3027-3036 (2001)
PubMed id: 11258916  
Z.Zhu, J.J.Dumas, S.E.Lietzke, D.G.Lambright.
Monomeric Rab GTPases function as ubiquitous regulators of intracellular membrane trafficking. Mss4, an evolutionarily conserved Rab accessory factor, promotes nucleotide release from exocytic but not endocytic Rab GTPases. Here we describe the results of a high-resolution crystallographic and mutational analysis of Mss4. The 1.65 A crystal structure of Mss4 reveals a network of direct and water-mediated interactions that stabilize a partially exposed structural subdomain derived from four highly conserved but nonconsecutive sequence elements. The conserved subdomain contains the invariant cysteine residues required for Zn2+ binding as well as the residues implicated in the interaction with Rab GTPases. A strictly conserved DPhiPhi motif, consisting of an invariant aspartic acid residue (Asp 73) followed by two bulky hydrophobic residues (Met 74 and Phe 75), encodes a prominently exposed 3(10) helical turn in which the backbone is well-ordered but the side chains of the conserved residues are highly exposed and do not engage in intramolecular interactions. Substitution of any of these residues with alanine dramatically impairs nucleotide release activity toward Rab3A, indicating that the DPhiPhi motif is a critical element of the Rab interaction epitope. In particular, mutation of Phe 75 results in a defect as severe as that observed for mutation of Asp 96, which is located near the zinc binding site at the opposite end of the conserved subdomain. Despite severe defects, however, none of the mutant proteins is catalytically dead. Taken together, the results suggest a concerted mechanism in which distal elements of the conserved Rab interaction epitope cooperatively facilitate nucleotide release.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21194374 V.Wixler, L.Wixler, A.Altenfeld, S.Ludwig, R.S.Goody, and A.Itzen (2011).
Identification and characterisation of novel Mss4-binding Rab GTPases.
  Biol Chem, 392, 239-248.  
17450153 A.Delprato, and D.G.Lambright (2007).
Structural basis for Rab GTPase activation by VPS9 domain exchange factors.
  Nat Struct Mol Biol, 14, 406-412.
PDB code: 2ot3
17585939 C.Sachse, J.Z.Chen, P.D.Coureux, M.E.Stroupe, M.Fändrich, and N.Grigorieff (2007).
  J Mol Biol, 371, 812-835.
PDB code: 2om3
  16511278 A.Itzen, N.Bleimling, A.Ignatev, O.Pylypenko, and A.Rak (2006).
Purification, crystallization and preliminary X-ray crystallographic analysis of mammalian MSS4-Rab8 GTPase protein complex.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 113-116.  
16541104 A.Itzen, O.Pylypenko, R.S.Goody, K.Alexandrov, and A.Rak (2006).
Nucleotide exchange via local protein unfolding--structure of Rab8 in complex with MSS4.
  EMBO J, 25, 1445-1455.
PDB code: 2fu5
16006164 V.Thayanithy, and T.Venugopal (2005).
Evolution and expression of translationally controlled tumour protein (TCTP) of fish.
  Comp Biochem Physiol B Biochem Mol Biol, 142, 8.  
15339665 A.Delprato, E.Merithew, and D.G.Lambright (2004).
Structure, exchange determinants, and family-wide rab specificity of the tandem helical bundle and Vps9 domains of Rabex-5.
  Cell, 118, 607-617.
PDB code: 1txu
12105226 D.J.Strick, D.M.Francescutti, Y.Zhao, and L.A.Elferink (2002).
Mammalian suppressor of Sec4 modulates the inhibitory effect of Rab15 during early endocytosis.
  J Biol Chem, 277, 32722-32729.  
11938352 W.T.Lowther, H.Weissbach, F.Etienne, N.Brot, and B.W.Matthews (2002).
The mirrored methionine sulfoxide reductases of Neisseria gonorrhoeae pilB.
  Nat Struct Biol, 9, 348-352.
PDB code: 1l1d
11567160 Y.W.Chen (2001).
Solution solution: using NMR models for molecular replacement.
  Acta Crystallogr D Biol Crystallogr, 57, 1457-1461.  