Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=24511139
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Structure of the kidney slit diaphragm adapter protein CD2-associated protein as
determined with electron microscopy
#MMPMID24511139
Adair BD
; Altintas MM
; Möller CC
; Arnaout MA
; Reiser J
J Am Soc Nephrol
2014[Jul]; 25
(7
): 1465-73
PMID24511139
show ga
CD2-associated protein (CD2AP) is a multidomain scaffolding protein that has a
critical role in renal function. CD2AP is expressed in glomerular podocytes at
the slit diaphragm, a modified adherens junction that comprises the protein
filtration barrier of the kidney, and interacts with a number of protein ligands
involved in cytoskeletal remodeling, membrane trafficking, cell motility, and
cell survival. The structure of CD2AP is unknown. We used electron microscopy and
single particle image analysis to determine the three-dimensional structure of
recombinant full-length CD2AP and found that the protein is a tetramer in
solution. Image reconstruction of negatively stained protein particles generated
a structure at 21 Å resolution. The protein assumed a roughly spherical, very
loosely packed structure. Analysis of the electron density map revealed that
CD2AP consists of a central coiled-coil domain, which forms the tetramer
interface, surrounded by four symmetry-related motifs, each containing three
globular domains corresponding to the three SH3 domains. The spatial organization
exposes the binding sites of all 12 SH3 domains in the tetramer, allowing
simultaneous binding to multiple targets. Determination of the structure of CD2AP
provides novel insights into the biology of this slit diaphragm protein and lays
the groundwork for characterizing the interactions between key molecules of the
slit diaphragm that control glomerular filtration.
free
free
free
