1mb8 | pdb_00001mb8
Crystal Structure of the actin binding domain of plectin
Structural highlights
Disease[PLEC_HUMAN] Defects in PLEC are the cause of epidermolysis bullosa simplex with pyloric atresia (EBS-PA) [MIM:612138]. EBS-PA is an autosomal recessive genodermatosis characterized by severe skin blistering at birth and congenital pyloric atresia. Death usually occurs in infancy. This disorder is allelic to MD-EBS.[1] [2] [3] Defects in PLEC are the cause of epidermolysis bullosa simplex with muscular dystrophy (MD-EBS) [MIM:226670]. MD-EBS is an autosomal recessive disorder characterized by epidermal blister formation at the level of the hemidesmosome and associated with late-onset muscular dystrophy. Defects in PLEC are the cause of epidermolysis bullosa simplex Ogna type (O-EBS) [MIM:131950]; also called epidermolysis bullosa simplex 1. O-EBS is a form of intraepidermal epidermolysis bullosa characterized by generalized skin bruising, skin fragility with non-scarring blistering and small hemorrhagic blisters on hands. At the ultrastructural level, it is differentiated from classical cases of K-EBS, WC-EBS and DM-EBS, by the occurrence of blisters originating in basal cells above hemidesmosomes, and abnormal hemidesmosome intracellular attachment plates. Defects in PLEC are the cause of limb-girdle muscular dystrophy type 2Q (LGMD2Q) [MIM:613723]. An autosomal recessive degenerative myopathy characterized by early childhood onset of proximal muscle weakness. Note=A 9 bp deletion containing the initiation codon in exon 1f of PLEC have been found in limb-girdle muscular dystrophy patients. The mutation results in deficient expression of isoform 9 and disorganization of the myofibers, without any effect on the skin.[4] [5] Function[PLEC_HUMAN] Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofibers integrity.[6] [7] 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 PubMedPlectin is a widely expressed cytoskeletal linker. Here we report the crystal structure of the actin binding domain of plectin and show that this region is sufficient for interaction with F-actin or the cytoplasmic region of integrin alpha6beta4. The structure is formed by two calponin homology domains arranged in a closed conformation. We show that binding to F-actin induces a conformational change in plectin that is inhibited by an engineered interdomain disulfide bridge. A two-step induced fit mechanism involving binding and subsequent domain rearrangement is proposed. In contrast, interaction with integrin alpha6beta4 occurs in a closed conformation. Competitive binding of plectin to F-actin and integrin alpha6beta4 may rely on the observed alternative binding mechanisms and involve both allosteric and steric factors. Structural and functional analysis of the actin binding domain of plectin suggests alternative mechanisms for binding to F-actin and integrin beta4.,Garcia-Alvarez B, Bobkov A, Sonnenberg A, de Pereda JM Structure. 2003 Jun;11(6):615-25. PMID:12791251[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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