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PROFILIN BINDS PROLINE-RICH LIGANDS IN TWO DISTINCT AMIDE BACKBONE ORIENTATIONS
Structural highlights
DiseasePROF1_HUMAN Defects in PFN1 are the cause of amyotrophic lateral sclerosis 18 (ALS18) [MIM:614808. A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.[1] FunctionPROF1_HUMAN Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR.[2] 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 PubMedThe actin regulatory protein profilin is targeted to specific cellular regions through interactions with highly proline-rich motifs embedded within its binding partners. New X-ray crystallographic results demonstrate that profilin, like SH3 domains, can bind proline-rich ligands in two distinct amide backbone orientations. By further analogy with SH3 domains, these data suggest that non-proline residues in profilin ligands may dictate the polarity and register of binding, and the detailed organization of the assemblies involving profilin. This degeneracy may be a general feature of modules that bind proline-rich ligands, including WW and EVH1 domains, and has implications for the assembly and activity of macromolecular complexes involved in signaling and the regulation of the actin cytoskeleton. Profilin binds proline-rich ligands in two distinct amide backbone orientations.,Mahoney NM, Rozwarski DA, Fedorov E, Fedorov AA, Almo SC Nat Struct Biol. 1999 Jul;6(7):666-71. PMID:10404225[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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