3CI5

Complex of Phosphorylated Dictyostelium Discoideum Actin with Gelsolin

Summary for 3CI5

• Entry DOI: 10.2210/pdb3ci5/pdb
• Related: 1NM1 3CHW 3CIP
• Descriptor: Major actin, Gelsolin, MAGNESIUM ION, ... (8 entities in total)
• Functional Keywords: actin, gelsolin, dictyostelium discoideum, phosphorylated tyrosine, actin-associated protein, methyl histidine, atp-binding, cytoskeleton, nucleotide-binding, phosphoprotein, structural protein, actin capping, actin-binding, alternative initiation, amyloid, disease mutation, secreted
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm, cytoskeleton: P07830; Isoform 2: Cytoplasm, cytoskeleton. Isoform 1: Secreted: P06396
• Total number of polymer chains: 2
• Total formula weight: 57943.05

Authors

Baek, K.,Dominguez, R. (deposition date: 2008-03-10, release date: 2008-08-19, Last modification date: 2023-11-15)

Primary citation

Baek, K.,Liu, X.,Ferron, F.,Shu, S.,Korn, E.D.,Dominguez, R.
Modulation of actin structure and function by phosphorylation of Tyr-53 and profilin binding.
Proc.Natl.Acad.Sci.Usa, 105:11748-11753, 2008

PubMed Abstract: On starvation, Dictyostelium cells aggregate to form multicellular fruiting bodies containing spores that germinate when transferred to nutrient-rich medium. This developmental cycle correlates with the extent of actin phosphorylation at Tyr-53 (pY53-actin), which is low in vegetative cells but high in viable mature spores. Here we describe high-resolution crystal structures of pY53-actin and unphosphorylated actin in complexes with gelsolin segment 1 and profilin. In the structure of pY53-actin, the phosphate group on Tyr-53 makes hydrogen-bonding interactions with residues of the DNase I-binding loop (D-loop) of actin, resulting in a more stable conformation of the D-loop than in the unphosphorylated structures. A more rigidly folded D-loop may explain some of the previously described properties of pY53-actin, including its increased critical concentration for polymerization, reduced rates of nucleation and pointed end elongation, and weak affinity for DNase I. We show here that phosphorylation of Tyr-53 inhibits subtilisin cleavage of the D-loop and reduces the rate of nucleotide exchange on actin. The structure of profilin-Dictyostelium-actin is strikingly similar to previously determined structures of profilin-beta-actin and profilin-alpha-actin. By comparing this representative set of profilin-actin structures with other structures of actin, we highlight the effects of profilin on the actin conformation. In the profilin-actin complexes, subdomains 1 and 3 of actin close around profilin, producing a 4.7 degrees rotation of the two major domains of actin relative to each other. As a result, the nucleotide cleft becomes moderately more open in the profilin-actin complex, probably explaining the stimulation of nucleotide exchange on actin by profilin.

PubMed: 18689676
DOI: 10.1073/pnas.0805852105

Experimental method

X-RAY DIFFRACTION (1.7 Å)