@article {12934, title = {The expanding superfamily of gelsolin homology domain proteins}, journal = {Cytoskeleton}, volume = {70}, year = {2013}, month = {11/2013}, pages = {775-795}, type = {research}, chapter = {775}, abstract = {

The gelsolin homology (GH) domain has been found
to date exclusively in actin-binding proteins. In
humans, three copies of the domain are present in
CapG, five copies in supervillin, and six copies each in
adseverin, gelsolin, flightless I and the villins: villin,
advillin and villin-like protein. Caenorhabditis elegans
contains a four-GH-domain protein, GSNL-1. These
architectures are predicted to have arisen from gene
triplication followed by gene duplication to result in
the six-domain protein. The subsequent loss of one,
two or three domains produced the five-, four-, and
three-domain proteins, respectively. Here we conducted
BLAST and hidden Markov based searches of UniProt
and NCBI databases to identify novel gelsolin domain
containing proteins. The variety in architectures suggests
that the GH domain has been tested in many
molecular constructions during evolution. Of particular
note is flightless-like I protein (FLIIL1) from Entamoeba
histolytica, which combines a leucine rich
repeats (LRR) domain, seven GH domains, and a headpiece
domain, thus combining many of the features of
flightless I with those of villin or supervillin. As such,
the GH domain superfamily appears to have developed
along complex routes. The distribution of these proteins
was analyzed in the 343 completely sequenced
genomes, mapped onto the tree of life, and phylogenetic
trees of the proteins were constructed to gain
insight into their evolution.

}, keywords = {actin, flightless, gelsolin, supervillin, VILLIN}, doi = {10.1002/cm.21149}, author = {Ghoshdastider, U. and Popp, D. and Burtnick, L. D. and Robinson, R. C.} } @article {2653, title = {Helix Straightening as an Activation Mechanism in the Gelsolin Superfamily of Actin Regulatory Proteins}, journal = {Journal of Biological Chemistry}, volume = {284}, number = {32}, year = {2009}, note = {ISI Document Delivery No.: 478CCTimes Cited: 4Cited Reference Count: 23Wang, Hui Chumnarnsilpa, Sakesit Loonchanta, Anantasak Li, Qiang Kuan, Yang-Mei Robine, Sylvie Larsson, Marten Mihalek, Ivana Burtnick, Leslie D. Robinson, Robert C.}, month = {Aug}, pages = {21265-21269}, type = {Article}, abstract = {Villin and gelsolin consist of six homologous domains of the gelsolin/cofilin fold (V1-V6 and G1-G6, respectively). Villin differs from gelsolin in possessing at its C terminus an unrelated seventh domain, the villin headpiece. Here, we present the crystal structure of villin domain V6 in an environment in which intact villin would be inactive, in the absence of bound Ca2+ or phosphorylation. The structure of V6 more closely resembles that of the activated form of G6, which contains one bound Ca2+, rather than that of the calcium ion-free form of G6 within intact inactive gelsolin. Strikingly apparent is that the long helix in V6 is straight, as found in the activated form of G6, as opposed to the kinked version in inactive gelsolin. Molecular dynamics calculations suggest that the preferable conformation for this helix in the isolated G6 domain is also straight in the absence of Ca2+ and other gelsolin domains. However, the G6 helix bends in intact calcium ion-free gelsolin to allow interaction with G2 and G4. We suggest that a similar situation exists in villin. Within the intact protein, a bent V6 helix, when triggered by Ca2+, straightens and helps push apart adjacent domains to expose actin-binding sites within the protein. The sixth domain in this superfamily of proteins serves as a keystone that locks together a compact ensemble of domains in an inactive state. Perturbing the keystone initiates reorganization of the structure to reveal previously buried actin-binding sites.}, keywords = {BINDING PROTEINS, calcium, COMPLEX, DOMAINS, F-ACTIN, HEADPIECE, SITES, SWITCH, TERMINAL HALF, VILLIN}, isbn = {0021-9258}, url = {://000268564400020}, author = {Wang, H. and Chumnarnsilpa, S. and Loonchanta, A. and Li, Q. and Kuan, Y. M. and Robine, S. and Larsson, M. and Mihalek, I. and Burtnick, L. D. and Robinson, R. C.} } @article {3920, title = {The crystal structure of plasma gelsolin: Implications for actin severing, capping, and nucleation}, journal = {Cell}, volume = {90}, number = {4}, year = {1997}, note = {ISI Document Delivery No.: XT066Times Cited: 164Cited Reference Count: 50}, month = {Aug}, pages = {661-670}, type = {Article}, abstract = {The structure of gelsolin has been determined by crystallography and comprises six structurally related domains that, in a Ca2+-free environment, pack together to form a compact globular structure in which the putative actin-binding sequences are not sufficiently exposed to enable binding to occur. We propose that binding Ca2+ can release the connections that join the N- and C-terminal halves of gelsolin, enabling each half to bind actin relatively independently. Domain shifts are proposed in response to Ca2+ as bases for models of how gelsolin acts to sever, cap, or nucleate F-actin filaments. The structure also invites discussion of polyphosphoinositide binding to segment 2 and suggests how mutation at Asp-187 could initiate a series of events that lead to deposition of amyloid plaques, as observed in victims of familial amyloidosis (Finnish type).}, keywords = {AMYLOIDOSIS, BINDING DOMAIN, calcium, DEFINITION, F-ACTIN, FILAMENT, IDENTIFICATION, PROTEIN, SEQUENCE, VILLIN}, isbn = {0092-8674}, url = {://A1997XT06600010}, author = {Burtnick, L. D. and Koepf, E. K. and Grimes, J. and Jones, E. Y. and Stuart, D. I. and McLaughlin, P. J. and Robinson, R. C.} }