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

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

Cell

journal_title

Cell

authors

Heo WD,Meyer T

doi

10.1016/s0092-8674(03)00315-5

subject

Has Abstract

pub_date

2003-05-02 00:00:00

pages

315-28

issue

3

eissn

0092-8674

issn

1097-4172

pii

S0092867403003155

journal_volume

113

pub_type

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