Bacterial cold shock proteins (Csps) are over expressed as response to cold stress They have a role in transcriptional and translational events due to their ability to bind single stranded (ss) nucleic acids Csps so far characterized show similar structures with a closed five stranded antiparallel beta-barrel Here we report a structural and functional study of cold shock protein A from Mycobacterium tuberculosis MTB-CspA Structural investigations by CD and NMR reveal that MTB-CspA is less ordered than expected and is the least thermal stable cold shock protein so far characterized However electrophoretic mobility shift assays show that MTB-CspA is functionally active as it is able to bind oligonucleotides The dynamic behavior of MTB-CspA, compared to its homolog from Bacillus subtilis was investigated by molecular dynamics simulations at room and high temperatures Analysis of trajectories point to specific regions on beta 1 and beta 4 strands likely responsible for the higher structural fragility of MTB-CspA. Also they show that the nucleic-acid binding region of MTB-CspA is the least prone to unfolding a finding which explains the ability of MTB-CspA to exert its function (C) 2010 Elsevier Inc All rights reserved