Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 427, Issue 4, Pages 763-774Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2014.12.020
Keywords
DNA replication; DNA repair; cooperativity; regulation; simulations
Categories
Funding
- National Institutes of Health [GM030498]
- National Science Foundation [MCB1121867]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1121867] Funding Source: National Science Foundation
Ask authors/readers for more resources
The homotetrameric Escherichia coil single-stranded DNA binding protein (SSB) plays a central role in DNA replication, repair and recombination. Escherichia coil SSB can bind to long single-stranded DNA (ssDNA) in multiple binding modes using all four subunits [(SSB)(65) mode] or only two subunits [(SSB)(35) binding mode], with the binding mode preference regulated by salt concentration and SSB binding density. These binding modes display very different ssDNA binding properties with the (SSB)(35) mode displaying highly cooperative binding to ssDNA. SSB tetramers also bind an array of partner proteins, recruiting them to their sites of action. This is achieved through interactions with the last 9 amino acids (acidic tip) of the intrinsically disordered linkers (IDLs) within the four C-terminal tails connected to the ssDNA binding domains. Here, we show that the amino acid composition and length of the IDL affects the ssDNA binding mode preferences of SSB protein. Surprisingly, the number of IDLs and the lengths of individual IDLs together with the acidic tip contribute to highly cooperative binding in the (SSB)(35) binding mode. Hydrodynamic studies and atomistic simulations suggest that the Escherichia coil SSB IDLs show a preference for forming an ensemble of globular conformations, whereas the IDL from Plasmodium falciparum SSB forms an ensemble of more extended random coils. The more globular conformations correlate with cooperative binding. (C) 2014 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available