Sandbox Reserved 706
From Proteopedia
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The structure of the Slac2-a effector domain comprises three subdomains: SHD1, SHD2, and a zinc-binding subdomain that is flanked by the two SHDs. <ref>PMID:11856727</ref> | The structure of the Slac2-a effector domain comprises three subdomains: SHD1, SHD2, and a zinc-binding subdomain that is flanked by the two SHDs. <ref>PMID:11856727</ref> | ||
SHD1 is folded into a 66 A ° long helix α1, and SHD2 is composed of three helices (α3–α5). SHD1 and SHD2 interact with each other by making a coiled coil between α1 and α3–α5. In this coiled coil, α3 and α5 interact with α1 in an antiparallel manner (also see fidure 2). | SHD1 is folded into a 66 A ° long helix α1, and SHD2 is composed of three helices (α3–α5). SHD1 and SHD2 interact with each other by making a coiled coil between α1 and α3–α5. In this coiled coil, α3 and α5 interact with α1 in an antiparallel manner (also see fidure 2). | ||
| - | The zinc-binding subdomain contains four short ß strands (ß1–ß4) and loops including three short helices (α2, h1, and h2). The two zinc ions (Zn1 and Zn2) are each coordinated by four conserved cysteine residues: Cys64, Cys67, Cys89 | + | The zinc-binding subdomain contains four short ß strands (ß1–ß4) and loops including three short helices (α2, h1, and h2). The two zinc ions (Zn1 and Zn2) are each coordinated by four conserved cysteine residues: |
| + | <scene name='Sandbox_Reserved_706/Cys_64_67_89/1'>Cys64, Cys67, Cys89</scene> and Cys92 for Zn1 binding, and Cys81, Cys84, Cys104, and Cys107 for Zn2 binding. <ref>PMID:18940604</ref> | ||
Revision as of 19:52, 4 January 2013
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| 2zet, resolution 3.00Å () | |||||||||
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| Ligands: | , , , | ||||||||
| Non-Standard Residues: | |||||||||
| Gene: | Rab27b (Mus musculus), Slac2a (Mus musculus) | ||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum, TOPSAN | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Contents |
Structure
Structure of Rab27B
General informations:
To obtain structural information on the complex of mouse Rab27B and Slac-a, a C-terminally truncated form of the GTPase-deficient mutant Rab27B (Q78L) was used. In fact, full size of Rab27B is 218 amino acids long whereas the truncated form of Rab27B contains only the GTPase domain (residues 1 to 201). [1] [2]
Detailed structure:
The structure of Rab27B in the complex contains a central six stranded beta sheet (ß1-6) flanked by five alpha helices (α1–5). Like other Ras-like small GTPases, Rab27B binds with GTP and Mg2+ in the conserved nucleotide-binding site (also see figure 2). Rab27B adopt a globular form in the complex. The ß2 and ß3 loop(residues 55-64) and α3-ß5 loop (residues122-126) of Rab27B are both regions involved in Slac2-a binding. [3]
The complex Rab27B/Slac2-a can only be formed when Rab27B is in a GTP form. This can be explain because of the changing of shape between Rab27B in the GTP and GDP form. (See figure 3)
Rab27B–GTP adopts a compact monomer conformation, while an extended conformation was observed for GDP-bound Rab27B.
Switch 1 and switch 2 of Rab27B play an important role in this changing of conformation. In fact, switch 1 and 2 allow GTP binding by making hydrogen bond with its γ-phosphate, and this way also allow Slac2-a binding.(see next paragraph) But in the complex Rab27B/GDP switch 1 and switch 2 exist completely apart from the bound GDP, so that there are no inter-actions with Slac2-a and no binding.
Strucure Slac2-a
General informations:
Slac2-a is a fragment from Slp Homology Domain, residues 1-146 from Melanophilin molecule. This protein is also called Exophilin-3. [4] Slac2-a plays an important role in actin-based melanosome transport in mammalian. In fact, the actin-binding domain of Slac2-a/Melanophilin is required for melanosome distribution in melanocytes.[5]
To obtain structural information on the complex of mouse Rab27B/Slac2-a, a truncated form of Slac2-a was used. This fragment of Slac2-a is the minimum region (residue 1 to 146) of Slac2-a that specifically binds to the GTP-bound form of Rab27B.
Detailed structure:
The structure of the Slac2-a effector domain comprises three subdomains: SHD1, SHD2, and a zinc-binding subdomain that is flanked by the two SHDs. [6] SHD1 is folded into a 66 A ° long helix α1, and SHD2 is composed of three helices (α3–α5). SHD1 and SHD2 interact with each other by making a coiled coil between α1 and α3–α5. In this coiled coil, α3 and α5 interact with α1 in an antiparallel manner (also see fidure 2). The zinc-binding subdomain contains four short ß strands (ß1–ß4) and loops including three short helices (α2, h1, and h2). The two zinc ions (Zn1 and Zn2) are each coordinated by four conserved cysteine residues: and Cys92 for Zn1 binding, and Cys81, Cys84, Cys104, and Cys107 for Zn2 binding. [7]
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References
- ↑ Kukimoto-Niino M, Sakamoto A, Kanno E, Hanawa-Suetsugu K, Terada T, Shirouzu M, Fukuda M, Yokoyama S. Structural basis for the exclusive specificity of Slac2-a/melanophilin for the Rab27 GTPases. Structure. 2008 Oct 8;16(10):1478-90. PMID:18940604 doi:10.1016/j.str.2008.07.014
- ↑ http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zet
- ↑ Kukimoto-Niino M, Sakamoto A, Kanno E, Hanawa-Suetsugu K, Terada T, Shirouzu M, Fukuda M, Yokoyama S. Structural basis for the exclusive specificity of Slac2-a/melanophilin for the Rab27 GTPases. Structure. 2008 Oct 8;16(10):1478-90. PMID:18940604 doi:10.1016/j.str.2008.07.014
- ↑ http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zet
- ↑ Kuroda TS, Ariga H, Fukuda M. The actin-binding domain of Slac2-a/melanophilin is required for melanosome distribution in melanocytes. Mol Cell Biol. 2003 Aug;23(15):5245-55. PMID:12861011
- ↑ Fukuda M, Kuroda TS, Mikoshiba K. Slac2-a/melanophilin, the missing link between Rab27 and myosin Va: implications of a tripartite protein complex for melanosome transport. J Biol Chem. 2002 Apr 5;277(14):12432-6. Epub 2002 Feb 20. PMID:11856727 doi:10.1074/jbc.C200005200
- ↑ Kukimoto-Niino M, Sakamoto A, Kanno E, Hanawa-Suetsugu K, Terada T, Shirouzu M, Fukuda M, Yokoyama S. Structural basis for the exclusive specificity of Slac2-a/melanophilin for the Rab27 GTPases. Structure. 2008 Oct 8;16(10):1478-90. PMID:18940604 doi:10.1016/j.str.2008.07.014
