General Information

Database Accession: DI2100002

Name: Cytosolic dynein intermediate chain bound to Tctex-type dynein light chain (D. melanogaster)

PDB ID: 3fm7 PDB

Experimental method: X-ray (3.50 Å)

Source organism: Drosophila melanogaster

Proof of disorder: Confirmed

Primary publication of the structure:

Hall J, Karplus PA, Barbar E
Multivalency in the assembly of intrinsically disordered Dynein intermediate chain.
(2009) J. Biol. Chem. 284: 33115-21

PMID: 19759397 PubMed

Abstract:

Dynein light chains are thought to increase binding efficiency of dynein intermediate chain to both dynein heavy chain and dynactin, but their exact role is not clear. Isothermal titration calorimetry and x-ray crystallography reported herein indicate that multivalency effects underlie efficient dynein assembly and regulation. For a ternary complex of a 60-amino acid segment of dynein intermediate chain (IC) bound to two homodimeric dynein light chains Tctex1 and LC8, there is a 50-fold affinity enhancement for the second light chain binding. For a designed IC construct containing two LC8 sites, observed the 1000-fold enhancement reflects a remarkably pure entropic chelate effect of a magnitude commensurate with theoretical predictions. The lower enhancement in wild-type IC is attributed to unfavorable free energy changes associated with incremental interactions of IC with Tctex1. Our results show assembled dynein IC as an elongated, flexible polybivalent duplex, and suggest that polybivalency is an important general mechanism for constructing stable yet reversible and functionally versatile complexes.

Function and Biology Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.

Molecular function:

motor activity Catalysis of the generation of force resulting either in movement along a microfilament or microtubule, or in torque resulting in membrane scission, coupled to the hydrolysis of a nucleoside triphosphate. GeneOntology

protein binding Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules). GeneOntology

Biological process:

cell cycle The progression of biochemical and morphological phases and events that occur in a cell during successive cell replication or nuclear replication events. Canonically, the cell cycle comprises the replication and segregation of genetic material followed by the division of the cell, but in endocycles or syncytial cells nuclear replication or nuclear division may not be followed by cell division. GeneOntology

spermatid development The process whose specific outcome is the progression of a spermatid over time, from its formation to the mature structure. GeneOntology

axo-dendritic transport The directed movement of organelles or molecules along microtubules in neuron projections. GeneOntology

multicellular organism development The biological process whose specific outcome is the progression of a multicellular organism over time from an initial condition (e.g. a zygote or a young adult) to a later condition (e.g. a multicellular animal or an aged adult). GeneOntology

Cellular component:

cytoplasm All of the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. GeneOntology

cytoplasmic dynein complex Any dynein complex with a homodimeric dynein heavy chain core that catalyzes movement along a microtubule. Cytoplasmic dynein complexes participate in many cytoplasmic transport activities in eukaryotes, such as mRNA localization, intermediate filament transport, nuclear envelope breakdown, apoptosis, transport of centrosomal proteins, mitotic spindle assembly, virus transport, kinetochore functions, and movement of signaling and spindle checkpoint proteins. Some complexes participate in intraflagellar transport. Subunits associated with the dynein heavy chain mediate association between dynein heavy chain and cargoes, and may include light chains and light intermediate chains. GeneOntology

microtubule Any of the long, generally straight, hollow tubes of internal diameter 12-15 nm and external diameter 24 nm found in a wide variety of eukaryotic cells; each consists (usually) of 13 protofilaments of polymeric tubulin, staggered in such a manner that the tubulin monomers are arranged in a helical pattern on the microtubular surface, and with the alpha/beta axes of the tubulin subunits parallel to the long axis of the tubule; exist in equilibrium with pool of tubulin monomers and can be rapidly assembled or disassembled in response to physiological stimuli; concerned with force generation, e.g. in the spindle. GeneOntology

neuron projection A prolongation or process extending from a nerve cell, e.g. an axon or dendrite. GeneOntology

Structure Summary Structural annotations of the participating protein chains.

Entry contents: 3 distinct polypeptide molecules

Chains: C, A, B

Notes: Chains D, E and F were removed and chain C was truncated to include residues 109-123 (according to UniProt numbering) as chains A, B and the remaining region of chain C highlight the biologically relevant interaction.

Chain C

Name: Cytoplasmic dynein 1 intermediate chain Disordered Confirmed

Source organism: Drosophila melanogaster

Length: 15 residues

Sequence:Sequence according to PDB SEQRESNLSVYNVQATNIPPK

UniProtKB AC: Q24246 (positions: 109-123) UniProt Coverage: 2.3%

UniRef90 AC: UniRef90_Q24246 (positions: 109-123) UniRef90

Chain A

Name: Dynein light chain Tctex-type Ordered component

Source organism: Drosophila melanogaster

Length: 111 residues

Sequence:Sequence according to PDB SEQRESMDDSREESQFIVDDVSKTIKEAIETTIGGNAYQHDKVNNWTGQVVENCLTVLTKEQKPYKYIVTAMIMQKNGAGLHTASSCYWNNDTDGSCTVRWENKTMYCIVSVFGLAV

UniProtKB AC: Q94524 (positions: 1-111) UniProt Coverage: 100%

UniRef90 AC: UniRef90_Q94524 (positions: 1-111) UniRef90

Chain B

Name: Dynein light chain Tctex-type Ordered component

Source organism: Drosophila melanogaster

Length: 111 residues

Sequence:Sequence according to PDB SEQRESMDDSREESQFIVDDVSKTIKEAIETTIGGNAYQHDKVNNWTGQVVENCLTVLTKEQKPYKYIVTAMIMQKNGAGLHTASSCYWNNDTDGSCTVRWENKTMYCIVSVFGLAV

UniProtKB AC: Q94524 (positions: 1-111) UniProt Coverage: 100%

UniRef90 AC: UniRef90_Q94524 (positions: 1-111) UniRef90

Evidence Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding.

Chain C: Disordered Confirmed

The 109-135 region described in DisProt entry DP00605 and the 84-143 region described in IDEAL entry IID50052 cover 100% of the sequence present in the structure.

Chain A: Ordered component

The Tctex-1 dynein light chain domain involved in the interaction is known to adopt a stable structure in isolation in dimeric form (see Pfam domain PF03645). A solved structure of the domain dimer without bound ligands is represented by PDB ID 1ygt.

Chain B: Ordered component

The Tctex-1 dynein light chain domain involved in the interaction is known to adopt a stable structure in isolation in dimeric form (see Pfam domain PF03645). A solved structure of the domain dimer without bound ligands is represented by PDB ID 1ygt.

Related Structure(s) Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap).

No related structure was found in the Protein Data Bank.

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