Database Accession: DI1000131
Name: Cdc42 in complex with the GTPase-binding domain of WASP
PDB ID: 1cee
Experimental method: NMR
Source organism: Homo sapiens
Proof of disorder:
Kd: 7.70×10-08 M
Primary publication of the structure:
Abdul-Manan N, Aghazadeh B, Liu GA, Majumdar A, Ouerfelli O, Siminovitch KA, Rosen MK
Structure of Cdc42 in complex with the GTPase-binding domain of the 'Wiskott-Aldrich syndrome' protein.
(1999) Nature 399: 379-83
The Rho-family GTP-hydrolysing proteins (GTPases), Cdc42, Rac and Rho, act as molecular switches in signalling pathways that regulate cytoskeletal architecture, gene expression and progression of the cell cycle. Cdc42 and Rac transmit many signals through GTP-dependent binding to effector proteins containing a Cdc42/Rac-interactive-binding (CRIB) motif. One such effector, the Wiskott-Aldrich syndrome protein (WASP), is postulated to link activation of Cdc42 directly to the rearrangement of actin. Human mutations in WASP cause severe defects in haematopoletic cell function, leading to clinical symptoms of thrombocytopenia, immunodeficiency and eczema. Here we report the solution structure of a complex between activated Cdc42 and a minimal GTPase-binding domain (GBD) from WASP. An extended amino-terminal GBD peptide that includes the CRIB motif contacts the switch I, beta2 and alpha5 regions of Cdc42. A carboxy-terminal beta-hairpin and alpha-helix pack against switch II. The Phe-X-His-X2-His portion of the CRIB motif and the alpha-helix appear to mediate sensitivity to the nucleotide switch through contacts to residues 36-40 of Cdc42. Discrimination between the Rho-family members is likely to be governed by GBD contacts to the switch I and alpha5 regions of the GTPases. Structural and biochemical data suggest that GBD-sequence divergence outside the CRIB motif may reflect additional regulatory interactions with functional domains that are specific to individual effectors.
identical protein binding Interacting selectively and non-covalently with an identical protein or proteins.
protein domain specific binding Interacting selectively and non-covalently with a specific domain of a protein.
actin filament organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments. Includes processes that control the spatial distribution of actin filaments, such as organizing filaments into meshworks, bundles, or other structures, as by cross-linking.
blood coagulation The sequential process in which the multiple coagulation factors of the blood interact, ultimately resulting in the formation of an insoluble fibrin clot; it may be divided into three stages: stage 1, the formation of intrinsic and extrinsic prothrombin converting principle; stage 2, the formation of thrombin; stage 3, the formation of stable fibrin polymers.
Cdc42 protein signal transduction A series of molecular signals within the cell that are mediated by the Cdc42 protein switching to a GTP-bound active state.
Fc-gamma receptor signaling pathway involved in phagocytosis An Fc-gamma receptor signaling pathway that contributes to the endocytic engulfment of external particulate material by phagocytes.
epidermis development The process whose specific outcome is the progression of the epidermis over time, from its formation to the mature structure. The epidermis is the outer epithelial layer of an animal, it may be a single layer that produces an extracellular material (e.g. the cuticle of arthropods) or a complex stratified squamous epithelium, as in the case of many vertebrate species.
negative regulation of cellular component organization Any process that stops, prevents, or reduces the frequency, rate or extent of a process involved in the formation, arrangement of constituent parts, or disassembly of cell structures, including the plasma membrane and any external encapsulating structures such as the cell wall and cell envelope.
regulation of protein complex assembly Any process that modulates the frequency, rate or extent of protein complex assembly.
movement of cell or subcellular component The directed, self-propelled movement of a cell or subcellular component without the involvement of an external agent such as a transporter or a pore.
regulation of catalytic activity Any process that modulates the activity of an enzyme.
cellular component assembly The aggregation, arrangement and bonding together of a cellular component.
positive regulation of cytoskeleton organization Any process that activates or increases the frequency, rate or extent of the formation, arrangement of constituent parts, or disassembly of cytoskeletal structures.
establishment of localization in cell Any process, occuring in a cell, that localizes a substance or cellular component. This may occur via movement, tethering or selective degradation.
cytoskeleton Any of the various filamentous elements that form the internal framework of cells, and typically remain after treatment of the cells with mild detergent to remove membrane constituents and soluble components of the cytoplasm. The term embraces intermediate filaments, microfilaments, microtubules, the microtrabecular lattice, and other structures characterized by a polymeric filamentous nature and long-range order within the cell. The various elements of the cytoskeleton not only serve in the maintenance of cellular shape but also have roles in other cellular functions, including cellular movement, cell division, endocytosis, and movement of organelles.
extracellular exosome A membrane-bounded vesicle that is released into the extracellular region by fusion of the limiting endosomal membrane of a multivesicular body with the plasma membrane. Extracellular exosomes, also simply called exosomes, have a diameter of about 40-100 nm.
Entry contents: 2 distinct polypeptide molecules
Chains: B, A
Notes: No modifications of the original PDB file.
Name: Wiskott-Aldrich syndrome protein
Source organism: Homo sapiens
Length: 59 residues
Sequence:Sequence according to PDB SEQRESKKKISKADIGAPSGFKHVSHVGWDPQNGFDVNNLDPDLRSLFSRAGISEAQLTDAETSK
UniProtKB AC: P42768 (positions: 230-288)Coverage: 11.8%
UniRef90 AC: UniRef90_P42768 (positions: 230-288)
Name: Cell division control protein 42 homolog
Source organism: Homo sapiens
Length: 179 residues
Sequence:Sequence according to PDB SEQRESMQTIKCVVVGDGAVGKTCLLISYTTNKFPSEYVPTVFDNYAVTVMIGGEPYTLGLFDTAGQEDYDRLRPLSYPQTDVFLVCFSVVSPSSFENVKEKWVPEITHHCPKTPFLLVGTQIDLRDDPSTIEKLAKNKQKPITPETAEKLARDLKAVKYVECSALTQKGLKNVFDEAILAALEP
UniProtKB AC: P60953 (positions: 1-179)Coverage: 93.7%
UniRef90 AC: UniRef90_P60953 (positions: 1-179)
The interacting region of WASP (GBD/CRIB motif - PF00786) has been shown to be intrinsically disordered (PMID: 9660763 and PMID: 15821030). The 230-310 region described in IDEAL entry IID00269 covers 100% of the sequence present in the structure.
The ras domain involved in the interaction is known to adopt a stable structure in isolation (see Pfam domain PF00071). A solved monomeric structure of the domain from a homologous protein is represented by PDB ID 1aje.
No related structure was found in the Protein Data Bank.
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