| Structural highlights
Function
[GGA3_HUMAN] Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. Mediates the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (AC-LL) motif.[1] [RABE1_HUMAN] Rab effector protein acting as linker between gamma-adaptin, RAB4A and RAB5A. Involved in endocytic membrane fusion and membrane trafficking of recycling endosomes. Stimulates RABGEF1 mediated nucleotide exchange on RAB5A.[2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Adaptor proteins load transmembrane protein cargo into transport vesicles and serve as nexuses for the formation of large multiprotein complexes on the nascent vesicles. The gamma-adaptin ear (GAE) domains of the AP-1 adaptor protein complex and the GGA adaptor proteins recruit accessory proteins to these multiprotein complexes by binding to a hydrophobic motif. We determined the structure of the GAE domain of human GGA3 in complex with a peptide based on the DFGPLV sequence of the accessory protein Rabaptin-5 and refined it at a resolution of 2.2 A. The leucine and valine residues of the peptide are partly buried in two contiguous shallow, hydrophobic depressions. The anchoring phenylalanine is buried in a deep pocket formed by the aliphatic portions of two conserved arginine residues, along with an alanine and a proline, illustrating the unusual function of a cluster of basic residues in binding a hydrophobic motif.
Recognition of accessory protein motifs by the gamma-adaptin ear domain of GGA3.,Miller GJ, Mattera R, Bonifacino JS, Hurley JH Nat Struct Biol. 2003 Aug;10(8):599-606. PMID:12858162[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Puertollano R, Randazzo PA, Presley JF, Hartnell LM, Bonifacino JS. The GGAs promote ARF-dependent recruitment of clathrin to the TGN. Cell. 2001 Apr 6;105(1):93-102. PMID:11301005
- ↑ Stenmark H, Vitale G, Ullrich O, Zerial M. Rabaptin-5 is a direct effector of the small GTPase Rab5 in endocytic membrane fusion. Cell. 1995 Nov 3;83(3):423-32. PMID:8521472
- ↑ Nagelkerken B, Van Anken E, Van Raak M, Gerez L, Mohrmann K, Van Uden N, Holthuizen J, Pelkmans L, Van Der Sluijs P. Rabaptin4, a novel effector of the small GTPase rab4a, is recruited to perinuclear recycling vesicles. Biochem J. 2000 Mar 15;346 Pt 3:593-601. PMID:10698684
- ↑ Lippe R, Miaczynska M, Rybin V, Runge A, Zerial M. Functional synergy between Rab5 effector Rabaptin-5 and exchange factor Rabex-5 when physically associated in a complex. Mol Biol Cell. 2001 Jul;12(7):2219-28. PMID:11452015
- ↑ Deneka M, Neeft M, Popa I, van Oort M, Sprong H, Oorschot V, Klumperman J, Schu P, van der Sluijs P. Rabaptin-5alpha/rabaptin-4 serves as a linker between rab4 and gamma(1)-adaptin in membrane recycling from endosomes. EMBO J. 2003 Jun 2;22(11):2645-57. PMID:12773381 doi:http://dx.doi.org/10.1093/emboj/cdg257
- ↑ Miller GJ, Mattera R, Bonifacino JS, Hurley JH. Recognition of accessory protein motifs by the gamma-adaptin ear domain of GGA3. Nat Struct Biol. 2003 Aug;10(8):599-606. PMID:12858162 doi:10.1038/nsb953
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