| Structural highlights
Function
[SLA1_YEAST] Component of the PAN1 actin cytoskeleton-regulatory complex required for the internalization of endosomes during actin-coupled endocytosis. The complex links the site of endocytosis to the cell membrane-associated actin cytoskeleton. Mediates uptake of external molecules and vacuolar degradation of plasma membrane proteins. Plays a role in the proper organization of the cell membrane-associated actin cytoskeleton and promotes its destabilization.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15]
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 play important endocytic roles including recognition of internalization signals in transmembrane cargo. Sla1p serves as the adaptor for uptake of transmembrane proteins containing the NPFxD internalization signal, and is essential for normal functioning of the actin cytoskeleton during endocytosis. The Sla1p homology domain 1 (SHD1) within Sla1p is responsible for recognition of the NPFxD signal. This study presents the NMR structure of the NPFxD-bound state of SHD1 and a model for the protein-ligand complex. The alpha+beta structure of the protein reveals an SH3-like topology with a solvent-exposed hydrophobic ligand binding site. NMR chemical shift perturbations and effects of structure-based mutations on ligand binding in vitro define residues that are key for NPFxD binding. Mutations that abolish ligand recognition in vitro also abolish NPFxD-mediated receptor internalization in vivo. Thus, SHD1 is a novel functional domain based on SH3-like topology, which employs a unique binding site to recognize the NPFxD endocytic internalization signal. Its distant relationship with the SH3 fold endows this superfamily with a new role in endocytosis.
Structure of Sla1p homology domain 1 and interaction with the NPFxD endocytic internalization motif.,Mahadev RK, Di Pietro SM, Olson JM, Piao HL, Payne GS, Overduin M EMBO J. 2007 Apr 4;26(7):1963-71. Epub 2007 Mar 15. PMID:17363896[16]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Holtzman DA, Yang S, Drubin DG. Synthetic-lethal interactions identify two novel genes, SLA1 and SLA2, that control membrane cytoskeleton assembly in Saccharomyces cerevisiae. J Cell Biol. 1993 Aug;122(3):635-44. PMID:8335689
- ↑ Tang HY, Cai M. The EH-domain-containing protein Pan1 is required for normal organization of the actin cytoskeleton in Saccharomyces cerevisiae. Mol Cell Biol. 1996 Sep;16(9):4897-914. PMID:8756649
- ↑ Yang S, Ayscough KR, Drubin DG. A role for the actin cytoskeleton of Saccharomyces cerevisiae in bipolar bud-site selection. J Cell Biol. 1997 Jan 13;136(1):111-23. PMID:9008707
- ↑ Ayscough KR, Stryker J, Pokala N, Sanders M, Crews P, Drubin DG. High rates of actin filament turnover in budding yeast and roles for actin in establishment and maintenance of cell polarity revealed using the actin inhibitor latrunculin-A. J Cell Biol. 1997 Apr 21;137(2):399-416. PMID:9128251
- ↑ Ayscough KR, Eby JJ, Lila T, Dewar H, Kozminski KG, Drubin DG. Sla1p is a functionally modular component of the yeast cortical actin cytoskeleton required for correct localization of both Rho1p-GTPase and Sla2p, a protein with talin homology. Mol Biol Cell. 1999 Apr;10(4):1061-75. PMID:10198057
- ↑ Tang HY, Xu J, Cai M. Pan1p, End3p, and S1a1p, three yeast proteins required for normal cortical actin cytoskeleton organization, associate with each other and play essential roles in cell wall morphogenesis. Mol Cell Biol. 2000 Jan;20(1):12-25. PMID:10594004
- ↑ Howard JP, Hutton JL, Olson JM, Payne GS. Sla1p serves as the targeting signal recognition factor for NPFX(1,2)D-mediated endocytosis. J Cell Biol. 2002 Apr 15;157(2):315-26. Epub 2002 Apr 8. PMID:11940605 doi:http://dx.doi.org/10.1083/jcb.200110027
- ↑ Warren DT, Andrews PD, Gourlay CW, Ayscough KR. Sla1p couples the yeast endocytic machinery to proteins regulating actin dynamics. J Cell Sci. 2002 Apr 15;115(Pt 8):1703-15. PMID:11950888
- ↑ Dewar H, Warren DT, Gardiner FC, Gourlay CG, Satish N, Richardson MR, Andrews PD, Ayscough KR. Novel proteins linking the actin cytoskeleton to the endocytic machinery in Saccharomyces cerevisiae. Mol Biol Cell. 2002 Oct;13(10):3646-61. PMID:12388763 doi:http://dx.doi.org/10.1091/mbc.E02-05-0262
- ↑ Li H, Page N, Bussey H. Actin patch assembly proteins Las17p and Sla1p restrict cell wall growth to daughter cells and interact with cis-Golgi protein Kre6p. Yeast. 2002 Sep 30;19(13):1097-112. PMID:12237851 doi:http://dx.doi.org/10.1002/yea.904
- ↑ Rodal AA, Manning AL, Goode BL, Drubin DG. Negative regulation of yeast WASp by two SH3 domain-containing proteins. Curr Biol. 2003 Jun 17;13(12):1000-8. PMID:12814545
- ↑ Gourlay CW, Dewar H, Warren DT, Costa R, Satish N, Ayscough KR. An interaction between Sla1p and Sla2p plays a role in regulating actin dynamics and endocytosis in budding yeast. J Cell Sci. 2003 Jun 15;116(Pt 12):2551-64. Epub 2003 May 6. PMID:12734398 doi:http://dx.doi.org/10.1242/jcs.00454
- ↑ Stamenova SD, Dunn R, Adler AS, Hicke L. The Rsp5 ubiquitin ligase binds to and ubiquitinates members of the yeast CIN85-endophilin complex, Sla1-Rvs167. J Biol Chem. 2004 Apr 16;279(16):16017-25. Epub 2004 Feb 3. PMID:14761940 doi:http://dx.doi.org/10.1074/jbc.M313479200
- ↑ Rodal AA, Kozubowski L, Goode BL, Drubin DG, Hartwig JH. Actin and septin ultrastructures at the budding yeast cell cortex. Mol Biol Cell. 2005 Jan;16(1):372-84. Epub 2004 Nov 3. PMID:15525671 doi:http://dx.doi.org/10.1091/mbc.E04-08-0734
- ↑ Gardiner FC, Costa R, Ayscough KR. Nucleocytoplasmic trafficking is required for functioning of the adaptor protein Sla1p in endocytosis. Traffic. 2007 Apr;8(4):347-58. Epub 2007 Feb 7. PMID:17286805 doi:http://dx.doi.org/10.1111/j.1600-0854.2007.00534.x
- ↑ Mahadev RK, Di Pietro SM, Olson JM, Piao HL, Payne GS, Overduin M. Structure of Sla1p homology domain 1 and interaction with the NPFxD endocytic internalization motif. EMBO J. 2007 Apr 4;26(7):1963-71. Epub 2007 Mar 15. PMID:17363896
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