Structure of the profilin-poly-L-proline complex involved in morphogenesis and cytoskeletal regulation

Mahoney, Nicole M.; Janmey, Paul A.; Almo, Steven C.

doi:10.1038/nsb1197-953

Cited by 167 publications

(167 citation statements)

References 49 publications

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“…In recent years, the left-handed polyproline II (PPII) 1 helical conformation has been elevated from the status of a relatively rare and seemingly uninteresting secondary structure to one that is surprisingly common and of the utmost importance. This structure plays a central role in numerous vital processes including signal transduction, transcription, cell motility, and the immune response.…”

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confidence: 99%

Host−Guest Study of Left-Handed Polyproline II Helix Formation

et al. 2001

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The importance of the left-handed polyproline II (PPII) helical conformation has recently become apparent. This conformation generally is involved in two important functions: protein-protein interactions and structural integrity. PPII helices play vital roles in a variety of processes including signal transduction, transcription, and cell motility. Proline-rich regions of sequence are often assumed to adopt this structure. Remarkably, little is known about the physical determinants of this secondary structure type. In this study, we have explored the formation of PPII helices by a short poly(proline) peptide. In addition, the results from experiments used to determine the propensities for apolar residues, plus glycine, asparagine, and glutamine, to adopt this structure in a poly(proline)-based host peptide are reported here. Proline possesses the highest intrinsic propensity, with glutamine, alanine, and glycine having surprisingly high propensities.-Branched residues possess the lowest propensities of the residues examined. It is postulated that propensities possessed by apolar residues are due in part to peptide-solvent interactions, and that the remarkably high propensity possessed by glutamine may be due to a side chain to backbone hydrogen bond. These data are the first step toward a molecular understanding of the formation of this important, and yet little studied, secondary structure.In recent years, the left-handed polyproline II (PPII) 1 helical conformation has been elevated from the status of a relatively rare and seemingly uninteresting secondary structure to one that is surprisingly common and of the utmost importance. This structure plays a central role in numerous vital processes including signal transduction, transcription, cell motility, and the immune response. Proline-rich ligands of the cytoskeletal protein profilin (1), as well as those of the SH3, WW, and EVH1 protein interaction domains, are bound in this conformation (2). The peptide ligands of class II MHC molecules are also bound in the PPII conformation (3). PPII helices are major features of collagens (4) and plant cell wall proteins (5). The PPII helix is believed to be the dominant conformation for many proline-rich regions of sequence (PRRs) (6). Sequences not rich in proline also adopt this structure. For example, poly(lysine), poly(glutamate), and poly(aspartate) peptides form PPII helices (7). Around 2% of all residues in known protein structures are found in PPII helices at least four residues long (8, 9). As many as 10% of all residues are found in the PPII conformation, although not necessarily as part of PPII helices (10). PPII helices have also been hypothesized to be a major component of protein denatured states (11-14), giving them a role in a most fundamental process. Recently, Blanch et al. (15) have suggested that the PPII helix might be the precursor conformation in amyloid formation. Given the preceding, it is truly remarkable how little is known about the physical determinants of the PPII helical conformat...

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Host−Guest Study of Left-Handed Polyproline II Helix Formation

et al. 2001

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“…Whereas all of the maize pollen profilin isoforms have K d values of ‫572ف‬ M proline residues (Gibbon et al, 1997), ZmPRO4 has a substantially higher affinity, with a K d of 173 M proline residues. Eight of the most highly conserved residues in eukaryotic profilins ( Thorn et al, 1997), marked with asterisks in Figure 1, have been implicated in PLP binding by using mutagenesis (Björkegren et al, 1993;Haarer et al, 1993), nuclear magnetic resonance spectroscopy (Metzler et al, 1994; Domke et al, 1997), and x-ray crystallography (Mahoney et al, 1997). The hydroxyl group of tyrosine-6 was shown to interact directly with the backbone of the PLP peptide (Mahoney et al, 1997), and the Y6F mutation in human profilin I was shown to elute from PLP-agarose at a lower concentration of urea than did the wild-type protein (Sohn et al, 1995).…”

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Pollen Profilin Function Depends on Interaction with Proline-Rich Motifs

et al. 1998

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The actin binding protein profilin has dramatic effects on actin polymerization in vitro and in living cells. Plants have large multigene families encoding profilins, and many cells or tissues can express multiple profilin isoforms. Recently, we characterized several profilin isoforms from maize pollen for their ability to alter cytoarchitecture when microinjected into living plant cells and for their association with poly-L -proline and monomeric actin from maize pollen. In this study, we characterize a new profilin isoform from maize, which has been designated ZmPRO4, that is expressed predominantly in endosperm but is also found at low levels in all tissues examined, including mature and germinated pollen. The affinity of ZmPRO4 for monomeric actin, which was measured by two independent methods, is similar to that of the three profilin isoforms previously identified in pollen. In contrast, the affinity of ZmPRO4 for poly-L -proline is nearly twofold higher than that of native pollen profilin and the other recombinant profilin isoforms. When ZmPRO4 was microinjected into plant cells, the effect on actin-dependent nuclear position was significantly more rapid than that of another pollen profilin isoform, ZmPRO1. A gain-of-function mutant (ZmPRO1-Y6F) was created and found to enhance poly-L -proline binding activity and to disrupt cytoarchitecture as effectively as ZmPRO4. In this study, we demonstrate that profilin isoforms expressed in a single cell can have different effects on actin in living cells and that the poly-L -proline binding function of profilin may have important consequences for the regulation of actin cytoskeletal dynamics in plant cells. INTRODUCTIONThe male gametes of plants are delivered to the ovule by a unique mode of motility that is dependent on cellular morphogenesis of the pollen grain (reviewed in Bedinger and Edgerton, 1989;Mascarenhas, 1993;Taylor and Hepler, 1997). Mature pollen is a haploid multicellular structure consisting of a large vegetative cell and one generative cell or two sperm cells. The sperm are derived from a mitotic division of the generative cell that occurs before pollen maturation or during pollen tube extension. When a pollen grain lands on a receptive stigma, the vegetative cell forms a tipgrowing protuberance, the pollen tube, that extends down the transmitting tissue of the style toward the ovule. Remarkably, the growth rate of the maize pollen tube can exceed 1 cm/hr (Bedinger, 1992). The pollen tube delivers the sperm cells to the embryo sac, where they are deposited to fuse with the egg cell and central cell.Both pollen germination and pollen tube elongation are dependent on the actin cytoskeleton, as determined through studies with cytochalasins (reviewed in Pierson and Cresti, 1992;Taylor and Hepler, 1997). The actin cytoskeleton in pollen is highly dynamic, and dramatic rearrangements occur during pollen germination. Actin microfilaments focus on the germination aperture(s) before generation of the pollen tube and become arranged in long axial bundles t...

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“…Many more intracellular and extracellular modular protein domains have been identi®ed (reviewed by Bork et al, 1997). However, their ligands are as yet unknown, and signi®cant portions of the newly described modules so far seem to be con®ned to a limited number of specialized proteins that this domain will also bind its proline-rich ligand in a way in which individual proline residues contact the domain directly as well as serve a sca olding function to maintain the polyproline II helical structure, as was documented for ligands to SH3, WW and pro®lin (Yu et al, 1994;Macias et al, 1996;Mahoney et al, 1997).…”

Section: Degeneracy In The`protein Recognition Code'mentioning

confidence: 99%

“…Ligands for certain SH3 domains and ligands for group II WW domains, share a PPLP core (Sudol, 1996b). In addition, many physiological binders of pro®lin, including Mena, VASP, cdc12p, p140m Dia and Cappucino, all contain long runs of prolines interrupted or terminated by leucine (Mahoney et al, 1997). It is the PPLP core(s) of Mena that interact(s) with the WW domain of the FE65 adapter protein linked to the Alzheimer's beta amyloid precursor (Ermekova et al, 1997).…”

Section: Degeneracy In The`protein Recognition Code'mentioning

confidence: 99%

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From Src Homology domains to other signaling modules: proposal of the `protein recognition code'

1998

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The study of oncogenes has illuminated many aspects of cellular signaling. The delineation and characterization of protein modules exempli®ed by Src Homology domains has revolutionized our understanding of the molecular events underlying signal transduction pathways. Several well characterized intracellular modules which mediate protein-protein interactions, namely SH2, SH3, PH, PTB, EH, PDZ, EVH1 and WW domains, are directly involved in the multitude of membrane, cytoplasmic and nuclear processes in multicellular and/or unicellular organisms. The modular character of these protein domains and their cognate motifs, the universality of their molecular function, their widespread occurrence, and the speci®city as well as the degeneracy of their interactions have prompted us to propose the concept of the`protein recognition code'. By a parallel analogy to the universal genetic code, we propose here that there will be a ®nite set of precise rules to govern and predict protein-protein interactions mediated by modules. Several rules of the`protein recognition code' have already emerged.

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Structure of the profilin-poly-L-proline complex involved in morphogenesis and cytoskeletal regulation

Cited by 167 publications

References 49 publications

Host−Guest Study of Left-Handed Polyproline II Helix Formation

Host−Guest Study of Left-Handed Polyproline II Helix Formation

Pollen Profilin Function Depends on Interaction with Proline-Rich Motifs

From Src Homology domains to other signaling modules: proposal of the `protein recognition code'

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