Abstract

We review the most recent findings on human filamin structure, with particular emphasis on the relationships between structure, function, and interaction. Filamin is a cytoskeletal actin-binding protein and it is therefore crucial in providing cells with the necessary mechanical and dynamical properties. Filamentous actin cross-linking by filamin is regulated by a number of other proteins and the molecular mechanisms of this complex interaction network can be understood by highlighting the structural features of isolated filamin moieties and of their complexes with several partners. Here we describe first the structure-function relationships of the isolated filamin, its flexibility, and its dimerization mechanism. Secondly, we illustrate the structural mechanism with which filamin can recognize its partners, both the actin filaments and the regulatory proteins.

Keywords: Filamin, actin, actin-binding proteins, cystoskeleton, Z-disk, cytoskeletal actin-binding protein, cell's internal scaffold, chromosome separation, mitosis, meiosis, acto-myosin system, actinin, spectrin, N-terminal actin binding domain (ABD), calponin homology domains (CH), immunoglubulin-like domains, Dictyostelium discoideum filamin, mammalian filamin, FLNA, FLNB, FLNC, tumor necrosis, calcium-sensing receptor, glycoprotein Ib, pacemaker channel HCN1, dopamine D2, glutamate receptor type 7, calcitonin re-ceptor, potassium channel, integrin 7, to, myotilin, sarcolemma, transmembrane receptors, adapter proteins, myofibrillar myopathies, ectopic sites, Dimerization, Dictyostelium discoideum, C-Terminal Rod 2 Domains, N-Terminal Rod 1 Domains, Promiscuity and Fidelity