Abstract:
:Signaling proteins from the same family can have markedly different roles in a given cellular context. Here, we show that expression of one hundred constitutively active human small GTPases induced cell morphologies that fell into nine distinct classes. We developed an algorithm for pairs of classes that predicted amino acid positions that can be exchanged to create mutants with switched functionality. The algorithm was validated by creating switch-of-function mutants for Rac1, CDC42, H-Ras, RalA, Rap2B, and R-Ras3. Contrary to expectations, the relevant residues were mostly outside known interaction surfaces and were structurally far apart from each other. Our study shows that specificity in protein families can be explored by combining genome-wide experimental functional classification with the creation of switch-of-function mutants.
journal_name
Celljournal_title
Cellauthors
Heo WD,Meyer Tdoi
10.1016/s0092-8674(03)00315-5subject
Has Abstractpub_date
2003-05-02 00:00:00pages
315-28issue
3eissn
0092-8674issn
1097-4172pii
S0092867403003155journal_volume
113pub_type
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