title: Solution structure and dynamics of ADF/cofilin from Leishmania donovani.
abstract: Leishmania donovani ADF/cofilin (LdCof) is a novel member of ADF/cofilin family. LdCof depolymerizes, but does not co-sediment with, rabbit muscle actin filaments. Its F-actin depolymerizing activity is pH independent. Further, it possesses weak F-actin severing activity. In order to better understand its characteristic properties, we have determined the solution NMR structure of LdCof and have analyzed protein backbone dynamics from (15)N-relaxation measurements. The structure of LdCof possesses a conserved ADF/cofilin fold with a central mixed β-sheet consisting of six β-strands which is surrounded by five α-helices. LdCof structure has conserved G/F-actin binding site which includes the characteristic long kinked α-helix (α3). LdCof binds to rabbit muscle ADP-G-actin with 1:1 stoichiometry (K(d)∼0.2μM). The F-actin binding site is not well formed and analysis of (15)N-relaxation data shows that residues in the β4-β5 loop region and C-terminal are relatively flexible, which seems to be a determinant for the low F-actin severing activity of LdCof.
authors.affiliation: Molecular and Structural Biology Division, Central Drug Research Institute, Lucknow - 226 001, India.
authors.forename: Prem Prakash
authors.initials: PP
authors.lastname: Pathak
authors.forename: S V S R Krishna
authors.initials: SV
authors.lastname: Pulavarti
authors.forename: Anupam
authors.initials: A
authors.lastname: Jain
authors.forename: Amogh Anant
authors.initials: AA
authors.lastname: Sahasrabuddhe
authors.forename: Chhitar Mal
authors.initials: CM
authors.lastname: Gupta
authors.forename: Ashish
authors.initials: A
authors.lastname: Arora
mesh_terms: D051339:Actin Depolymerizing Factors / Q000737:chemistry*; D000199:Actins / Q000737:chemistry; D000818:Animals; D002151:Calorimetry; D007893:Leishmania donovani / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D018482:Muscle, Skeletal / Q000378:metabolism; D015800:Protozoan Proteins / Q000737:chemistry*; D011817:Rabbits
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D015800:Protozoan Proteins