Switch-of-function mutants based on morphology classification of Ras superfamily small GTPases

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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.
Publisher
CELL PRESS
Issue Date
2003
Language
English
Article Type
Article
Keywords

GTP-BINDING PROTEINS; ACTIN CYTOSKELETON; RHO-GTPASE; FAMILY; DOMAIN; PATHWAYS; CDC42; ACTIVATION; COMPLEX; MEMBER

Citation

CELL, v.113, no.3, pp.315 - 328

ISSN
0092-8674
URI
http://hdl.handle.net/10203/81676
Appears in Collection
BS-Journal Papers(저널논문)
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