IndraLab
Statements
sparser
"Given that the formation of Sos1-Grb2-Gab1 ternary signaling complex proceeds in a non-competitive manner [ xref ], the most straightforward interpretation of these salient observations is that the Sos1 peptide binds only to the nSH3 domain but not the cSH3 domain, while the Gab1 peptide binds only to the cSH3 domain in the context of full-length Grb2."
sparser
"While we have relied here on short peptides to mimic Sos1 and Gab1, due largely to inherent difficulties associated with isolation and purification of full-length Sos1 and Gab1 proteins, it should be noted that these peptides suffice par excellence for studying the binding of Sos1 and Gab1 to Grb2 using biophysical methods."
sparser
"Although these CD measurements are of highly qualitative nature and thus do not provide the physical basis of how the binding of Sos1 to the nSH3 domain may trigger a conformational change within Grb2 such that the nSH3 domain is only accessible to Gab1, the fact that Grb2 appears to be a highly flexible molecule by virtue of its ability to undergo discernable secondary and tertiary structural changes upon binding to Sos1 and Gab1 peptides nonetheless supports the notion that allostery is likely to play a central role in mediating communication between the nSH3 and cSH3 domains so as to allow the assembly of Sos1-Grb2-Gab1 ternary signaling complex in a non-competitive manner."
sparser
"Although efforts by others and us directed at the determination of X-ray or NMR structures of full-length Grb2 bound to Sos1 or Gab1 constructs of any sort over the past decade or so have met no success, presumably due to the transient nature of Sos1-Grb2-Gab1 complex, we have nonetheless made an attempt here to create a crude 3D structural model of how the binding of one molecule of Sos1 to the nSH3 domain may allosterically induce a conformational change within Grb2 such that the loading of a second molecule of Sos1 onto the cSH3 domain is blocked and, in so doing, allowing Gab1 access to the cSH3 domain in an exclusively non-competitive manner to generate the Sos1-Grb2-Gab1 ternary complex ( xref )."