Group:MUZIC:Plectin

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spinqualitylabelsall models actin binding domain(ABD) of plectin Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Contents 1 Introduction 2 Isoforms 3 Overall structure 4 Deposited structures in Protein Data Bank(PDB)

Introduction

Plectin is a multidomain protein with large size (>500kDa) and versatile binding properties, which abundantly expressed in a wide variety of mammalian tissues and cell types, combined with different binding partners. It has important functions in maintaining the mechanical stability of skin, skeletal muscle and heart.

Isoforms

The plectin gene has unusual 5'-end diversity, which is alternatively spliced into exon 2 and makes 11 kinds of isoforms. Expression level of isofroms is varied in tissues,and some of them are specifically expressed in brain,skeletal muscle and skin . ^[1].

Overall structure

Plectin can be divided in three main sections; a central coiled-coil rod domain, N and C-terminal globular region and exhibits a dumbbell like structure. C-terminal region is composed of 6 homologous repeating domains, and this region has a role in binding to intermediate filaments such as vimentin and cytokeratin ^[2]. N-terminal globular region contains actin binding domain (ABD) comprising two calponin homology.

Image:Plectin structure.jpg (Litjens, 2006)

Deposited structures in Protein Data Bank(PDB)

Only a few structures are available in PDB and focused on N-terminal region (actin binding domain and plakin domain.

1. Actin Binding Domain (ABD)

Plectin has a canonical actin binding domain in N-terminus, which is consisted of two calponin homology domain()^[3]. N-terminal domain of plectin containing ABD interacts with F-actin and regulates actin dynamics in vivo, additionally binding of plectin ABD to vimentin was also reported ^[4].

2. Plakin domain

The plakin domain is formed by an array of spectrin repeats (SR) and a Src-homology 3 (SH3), and harbors binding sites for junctional proteins. This region is adjacent to the actin-binding domain and is required for efficient binding to the integrin alpha6beta4 in hemidesmosomes.^[5]

spinqualitylabelsall models Crystal structure of SR4-SR5-SH3 regions in the plakin domain Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image 3.Integrin β4-Plectin complex The interaction between the integrin α6β4 and plectin is essential for the assembly and stability of hemidesmosomes, which are junctional adhesion complexes that anchor epithelial cells to the basement membrane.[6] spinqualitylabelsall models Insert caption here Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image References ↑ Fuchs P, Zorer M, Rezniczek GA, Spazierer D, Oehler S, Castanon MJ, Hauptmann R, Wiche G. Unusual 5' transcript complexity of plectin isoforms: novel tissue-specific exons modulate actin binding activity. Hum Mol Genet. 1999 Dec;8(13):2461-72. PMID:10556294 ↑ Foisner R, Wiche G. Structure and hydrodynamic properties of plectin molecules. J Mol Biol. 1987 Dec 5;198(3):515-31. PMID:3430617 ↑ Djinovic Carugo K, Banuelos S, Saraste M. Crystal structure of a calponin homology domain. Nat Struct Biol. 1997 Mar;4(3):175-9. PMID:9164454 ↑ Sevcik J, Urbanikova L, Kost'an J, Janda L, Wiche G. Actin-binding domain of mouse plectin. Crystal structure and binding to vimentin. Eur J Biochem. 2004 May;271(10):1873-84. PMID:15128297 doi:10.1111/j.1432-1033.2004.04095.x ↑ Ortega E, Buey RM, Sonnenberg A, de Pereda JM. The Structure of the Plakin Domain of Plectin Reveals a Non-canonical SH3 Domain Interacting with Its Fourth Spectrin Repeat. J Biol Chem. 2011 Apr 8;286(14):12429-38. Epub 2011 Feb 1. PMID:21288893 doi:10.1074/jbc.M110.197467 ↑ de Pereda JM, Lillo MP, Sonnenberg A. Structural basis of the interaction between integrin alpha6beta4 and plectin at the hemidesmosomes. EMBO J. 2009 Apr 22;28(8):1180-90. Epub 2009 Feb 26. PMID:19242489 doi:10.1038/emboj.2009.48