Contrasting factors on the kinetic path to protein complex formation diminish the effects of crowding agents.

Abstract:

:The crowded environment of cells poses a challenge for rapid protein-protein association. Yet, it has been established that the rates of association are similar in crowded and in dilute solutions. Here we probe the pathway leading to fast association between TEM1 β-lactamase and its inhibitor protein BLIP in crowded solutions. We show that the affinity of the encounter complex, the rate of final complex formation, and the structure of the transition state are similar in crowded solutions and in buffer. The experimental results were reproduced by calculations based on the transient-complex theory for protein association. Both experiments and calculations suggest that while crowding agents decrease the diffusion constant of the associating proteins, they also induce an effective excluded-volume attraction between them. The combination of the two opposing effects thus results in nearly identical overall association rates in diluted and crowded solutions.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Phillip Y,Harel M,Khait R,Qin S,Zhou HX,Schreiber G

doi

10.1016/j.bpj.2012.08.009

subject

Has Abstract

pub_date

2012-09-05 00:00:00

pages

1011-9

issue

5

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(12)00870-3

journal_volume

103

pub_type

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