Structure and functions of profilins

Abstract

Profilins are small actin-binding proteins found in eukaryotes and certain viruses that are involved in cell development, cytokinesis, membrane trafficking, and cell motility. Originally identified as an actin sequestering/ binding protein, profilin has been involved in actin polymerization dynamics. It catalyzes the exchange of ADP/ATP in actin and increases the rate of polymerization. Profilins also interact with polyphosphoinositides (PPI) and proline-rich domains containing proteins. Through its interaction with PPIs, profilin has been linked to signaling pathways between the cell membrane and the cytoskeleton, while its role in membrane trafficking has been associated with its interaction with proline-rich domain-containing proteins. Depending on the organism, profilin is present in a various number of isoforms. Four isoforms of profilin have been reported in higher organisms, while only one or two isoforms are expressed in single-cell organisms. The affinity of these isoforms for their ligands varies between isoforms and should therefore modulate their functions. However, the significance and the functions of the different isoforms are not yet fully understood. The structures of many profilin isoforms have been solved both in the presence and the absence of actin and poly-L-proline. These structural studies will greatly improve our understanding of the differences and similarities between the different profilins. Structural stability studies of different profilins are also shedding some light on our understanding of the profilin/ligand interactions. Profilin is a multifaceted protein for which a dramatic increase in potential functions has been found in recent years; as such, it has been implicated in a variety of physiological and pathological processes.

Proteomic Investigation of the Hippocampus in Prenatally Stressed Mice Implicates Changes in Membrane Trafficking, Cytoskeletal, and Metabolic Function

“…Our results showed expression changes in components of the cytoskeleton, such as NEFL, tubulin subunits, and INA. Furthermore, we observed downregulation of DPYSL2 and 3 and upregulation of PFN1, which may interfere with remodeling of the cytoskeleton during development, a requirement for axon guidance [52,53]. 14-3-3 protein epsilon, found to be downregulated by PS, plays an essential role in neuronal migration by interacting with NUDEL and DISC1 [54,55].…”

The phospholipid code: a key component of dying cell recognition, tumor progression and host–microbe interactions

“…For example, profilin, a PI(4,5)P 2 -binding protein involved in cytoskeletal restructuring and dynamic actin turnover, can competitively inhibit phospholipase C-mediated hydrolysis of PI(4,5)P 2 when bound. 104,135 are transported to the outer leaflet via floppases. 5 In addition to these ATP-dependent enzymes, scramblases, which can mediate ATP-independent bi-directional movement of lipids across the membrane, are also involved in maintaining phospholipid asymmetry.…”

Profilin, and Vascular Diseases

“…Radiography analyses of the structures of human profilin isoforms imply that the substitution of profilin-I S29 by Y29 in profilin-II participates in the higher affinity of profilin-II for proline-rich sequences (Nodelman et al, 1999). In spite of the similarity in the 3D structures of human profilin-I and -II, the surface characteristics, such as exposure of hydrophobic patches (Figure 2), and biochemical properties of each isoform are different (Krishnan & Moens, 2009). Fig.…”

“…1). The profilin polypeptide consists of 100-131amino acids (Krishnan & Moens, 2009) and it is folded into a central -pleated sheet formed of 5-7 antiparallel -strands (Schlüter et al, 1997). On one side, this core is flanked by N-and C-terminal -helices, with both termini next to each other, and on the opposed side by an extra -helix attached to either additional -helix or a small -strand (Schlüter et al, 1997) (Figure. It has been reported that there are three groups of ligands characterize profilins: (1) G-actin and actin-related proteins Schutt et al, 1989;Tobacman et al, 1983) (2) polyphosphoinositides (Lassing & Lindberg, 1985) (3) poly-L-proline (PLP) with the exception of Vaccinia profilin (Kaiser et al, 1989;Lindberg et al, 1988;Tanaka & Shibata 1985), existing either as a peptide or as a sequence motif in particular proteins.…”

“…1. Profilin-I isoforms from different organisms showing a similar helix (red) and strand (cyan) structure (PDB database: 1PFL, 1KOK, 2PRF, and 3NUL) with the loops highlighted in green, adapted from Krishnan & Moens, (2009) with permission.…”