1PWJ

Structure of the Monomeric 8-kDa Dynein Light Chain and Mechanism of Domain Swapped Dimer Assembly

Summary for 1PWJ

• Entry DOI: 10.2210/pdb1pwj/pdb
• Related: 1F3C 1F95 1F96 1PWK
• Descriptor: dynein light chain-2 (1 entity in total)
• Functional Keywords: dynein, dynein light chain, dimer-monomer equilibrium, domain swapping, contractile protein
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Cytoplasm, cytoskeleton: Q9D0M5
• Total number of polymer chains: 1
• Total formula weight: 10364.85

Authors

Wang, W.,Lo, K.W.-H.,Kan, H.-M.,Fan, J.-S.,Zhang, M. (deposition date: 2003-07-02, release date: 2003-10-21, Last modification date: 2024-05-29)

Primary citation

Wang, W.,Lo, K.W.-H.,Kan, H.-M.,Fan, J.-S.,Zhang, M.
Structure of the Monomeric 8-kDa Dynein Light Chain and Mechanism of the Domain-swapped Dimer Assembly
J.Biol.Chem., 278:41491-41499, 2003

PubMed Abstract: The 8-kDa light chain of dynein (DLC8) is ubiquitously expressed in various cell types. Other than serving as a light chain of the dynein complexes, this highly conserved protein has been shown to bind a larger number of proteins with diverse biological functions. DLC8 forms a homodimer via three-dimensional domain swapping of an internal beta-strand (the beta2-strand) at neutral pH. The protein undergoes non-reversible dimer-to-monomer dissociation when the pH value of the protein solution decreases. The three-dimensional structure of the DLC8 monomer determined by NMR spectroscopy at pH 3.0 showed that the protein is well folded. The major conformational change accompanied by dimer dissociation is in the beta2-strand of the protein, which undergoes transition from a beta-strand to a nascent alpha-helix. The monomer form of DLC8 is not capable of binding to target proteins. Insertion of two flexible amino acid residues in the tight beta1/beta2-loop dramatically stabilized the monomer conformation of the protein. NMR studies showed that the mutation altered the conformation as well as the three-dimensional domain swapping-mediated assembly of the DLC8 dimer. The mutant DLC8 was unable to bind to its targets even at physiological pH. The three-dimensional structure of the mutant protein in its monomeric form provides the structural basis of the mutation-induced stabilization of the monomer conformation. Based on the experimental data, we conclude that the formation of the beta2-strand swapping-mediated dimer is mandatory for the structure and function of DLC8. We further note that the DLC8 dimer represents a novel mode of three-dimensional domain swapping.

PubMed: 12904292
DOI: 10.1074/jbc.M307118200

Experimental method

SOLUTION NMR