PDBsum entry 1k8r

Signaling protein

PDB id: 1k8r

Contents

Protein chains

166 a.a. *

82 a.a. *

Ligands

GNP

Metals

_MG

* Residue conservation analysis

PDB id:

1k8r

Name:

Signaling protein

Title:

Crystal structure of ras-bry2rbd complex

Structure:

Transforming protein p21/h-ras-1. Chain: a. Fragment: gtp-binding/catalytic domain, residues 1-166. Engineered: yes. Protein kinase byr2. Chain: b. Fragment: ras binding domain (rbd), residues 71-180. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hras or hras1. Expressed in: escherichia coli. Expression_system_taxid: 562. Schizosaccharomyces pombe. Fission yeast. Organism_taxid: 4896.

Biol. unit:

Tetramer (from PQS)

Resolution:

3.00Å R-factor: 0.235 R-free: 0.305

Authors:

K.Scheffzek,P.Gruenewald,S.Wohlgemuth,W.Kabsch,H.Tu,M.Wigler, A.Wittinghofer,C.Herrmann

Key ref:

K.Scheffzek et al. (2001). The Ras-Byr2RBD complex: structural basis for Ras effector recognition in yeast. Structure, 9, 1043-1050. PubMed id: 11709168 DOI: 10.1016/S0969-2126(01)00674-8

Date:

25-Oct-01 Release date: 13-Mar-02

Protein chain

P01112  (RASH_HUMAN) -  GTPase HRas from Homo sapiens

Seq: 189 a.a.

Struc: 166 a.a.

Protein chain

P28829  (BYR2_SCHPO) -  Protein kinase byr2 from Schizosaccharomyces pombe (strain 972 / ATCC 24843)

Seq: 659 a.a.

Struc: 82 a.a.

Enzyme reactions

• Enzyme class 2: Chain A: E.C.3.6.5.2 - small monomeric GTPase.
• Reaction: GTP + H2O = GDP + phosphate + H⁺

GTP + H2O = GDP (Bound ligand (Het Group name = GNP) matches with 81.82% similarity) + phosphate + H(+)

• Enzyme class 3: Chain B: E.C.2.7.11.25 - mitogen-activated protein kinase kinase kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] (Bound ligand (Het Group name = GNP) matches with 78.79% similarity) + ADP + H(+)

L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] (Bound ligand (Het Group name = GNP) matches with 78.79% similarity) + ADP + H(+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/S0969-2126(01)00674-8

Structure 9:1043-1050 (2001)

PubMed id: 11709168

The Ras-Byr2RBD complex: structural basis for Ras effector recognition in yeast.

K.Scheffzek, P.Grünewald, S.Wohlgemuth, W.Kabsch, H.Tu, M.Wigler, A.Wittinghofer, C.Herrmann.

ABSTRACT

BACKGROUND: The small GTP binding protein Ras has important roles in cellular growth and differentiation. Mutant Ras is permanently active and contributes to cancer development. In its activated form, Ras interacts with effector proteins, frequently initiating a kinase cascade. In the lower eukaryotic Schizosaccharomyces pombe, Byr2 kinase represents a Ras target that in terms of signal-transduction hierarchy can be considered a homolog of mammalian Raf-kinase. The activation mechanism of protein kinases by Ras is not understood, and there is no detailed structural information about Ras binding domains (RBDs) in nonmammalian organisms. RESULTS: The crystal structure of the Ras-Byr2RBD complex at 3 A resolution shows a complex architecture similar to that observed in mammalian homologous systems, with an interprotein beta sheet stabilized by predominantly polar interactions between the interacting components. The C-terminal half of the Ras switch I region contains most of the contact anchors, while on the Byr2 side, a number of residues from topologically distinct regions are involved in complex stabilization. A C-terminal helical segment, which is not present in the known mammalian homologous systems and which is part of the auto-inhibitory region, has an additional binding site outside the switch I region. CONCLUSIONS: The structure of the Ras-Byr2 complex confirms the Ras binding module as a communication element mediating Ras-effector interactions; the Ras-Byr2 complex is also conserved in a lower eukaryotic system like yeast, which is in contrast to other small GTPase families. The extra helical segment might be involved in kinase activation.

Selected figure(s)

Figure 1.
Figure 1. The Ras-Byr2RBD Complex(a) Ribbon representation showing Byr2RBD on the left and Ras on the right. Switch I is shown in light blue, switch II is in dark blue, and the nucleotide is in pink. The presumed helical segment in the middle of the RBD is indicated as a dashed wavy line.(b) Structure-based sequence alignment of the RBDs from Raf [13], PI3-kinase [17], RalGDS [7], and Byr2 (this work), done with the program STAMP [72]. Assignment of secondary structure elements according to the program DSSP [73] is included for Byr2RBD; dashed lines indicate disordered regions. Structurally related regions are boxed and residues conserved as hydrophobic or polar amino acids are in yellow and red, respectively. Residues involved in the interaction with Ras are marked with green dots

The above figure is reprinted by permission from Cell Press: Structure (2001, 9, 1043-1050) copyright 2001.

Figure was selected by an automated process.