PDBsum entry 2a91

Signaling protein,transferase,membrane p

PDB id: 2a91

Contents

Protein chain

506 a.a. *

Ligands

NAG-NAG

NAG ×2

Waters ×134

* Residue conservation analysis

PDB id:

2a91

Name:

Signaling protein,transferase,membrane p

Title:

Crystal structure of erbb2 domains 1-3

Structure:

Receptor tyrosine-protein kinase erbb-2. Chain: a. Fragment: residues 1-510 + flag peptide. Synonym: p185erbb2. C-erbb-2. Neu proto-oncogene. Tyrosine kinase- type cell surface receptor her2. Mln 19. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: erbb2, her2, neu, ngl. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell: hampster ovary cells.

Resolution:

2.50Å R-factor: 0.226 R-free: 0.264

Authors:

T.P.J.Garrett,N.M.Mckern,M.Lou,T.C.Elleman,T.E.Adams,G.O.Lovrecz, M.Kofler,R.N.Jorissen,E.C.Nice,A.W.Burgess

Key ref:

T.P.Garrett et al. (2003). The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors. Mol Cell, 11, 495-505. PubMed id: 12620236 DOI: 10.1016/S1097-2765(03)00048-0

Date:

11-Jul-05 Release date: 26-Jul-05

Protein chain

P04626  (ERBB2_HUMAN) -  Receptor tyrosine-protein kinase erbB-2 from Homo sapiens

Seq: 1255 a.a.

Struc: 506 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] (Bound ligand (Het Group name = NAG) matches with 41.38% similarity) + ADP + H(+)

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

Added reference

DOI no: 10.1016/S1097-2765(03)00048-0

Mol Cell 11:495-505 (2003)

PubMed id: 12620236

The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors.

T.P.Garrett, N.M.McKern, M.Lou, T.C.Elleman, T.E.Adams, G.O.Lovrecz, M.Kofler, R.N.Jorissen, E.C.Nice, A.W.Burgess, C.W.Ward.

ABSTRACT

ErbB2 does not bind ligand, yet appears to be the major signaling partner for other ErbB receptors by forming heteromeric complexes with ErbB1, ErbB3, or ErbB4. The crystal structure of residues 1-509 of ErbB2 at 2.5 A resolution reveals an activated conformation similar to that of the EGFR when complexed with ligand and very different from that seen in the unactivated forms of ErbB3 or EGFR. The structure explains the inability of ErbB2 to bind known ligands and suggests why ErbB2 fails to form homodimers. Together, the data suggest a model in which ErbB2 is already in the activated conformation and ready to interact with other ligand-activated ErbB receptors.

Selected figure(s)

Figure 1.
Figure 1. Comparison of ErbB2(1–509) with sEGFR501 and sErbB3(1–621)Helices are indicated by curled, red ribbons and β strands by broad arrows. The blue, green, and yellow β strands depict the three prominent parallel β sheets within the L1 and L2 domains. The β strands in the cys-rich domains are colored orange, except for those in the CR1 loop which are colored brown. The side chains of disulfide-linked cysteine residues are depicted as yellow sticks. Structure sources are: sEGFR501 (Garrett et al., 2002); sErbB3 (Cho and Leahy, 2002). Secondary structure for ErbB3 is as defined by the authors.

Figure 4.
Figure 4. Molecular Surfaces Showing Ligand Binding and L Domain Contact Regions(A) The L1 domain contact residues are colored red for atoms which contact ErbB2 L2, blue for atoms equivalent to those in EGFR which bind TGFα, and purple for atoms in both regions. Arg13 (yellow) lies in the overlap region and would prevent ligand binding. The orientation of the L1 domain is shown in the insert ribbon diagram (bottom left), colored as in Figure 1. Reference to Figure 2 allows the nature of the contact residues and their location in the structure to be identified.(B) The L2 domain contact residues are colored red for atoms which contact ErbB2 L1 domain, blue for atoms equivalent to those in EGFR, which bind TGFα, and purple for atoms in both regions. The orientation of the L2 domain is shown in the insert ribbon diagram (bottom center), colored as in Figure 1. Reference to Figure 2 allows the nature of the contact residues and their location in the structure to be identified.

The above figures are reprinted by permission from Cell Press: Mol Cell (2003, 11, 495-505) copyright 2003.

Figures were selected by an automated process.