PDBsum entry 2ffw

Ligase

PDB id: 2ffw

Contents

Protein chain

78 a.a. *

Metals

_ZN ×2

* Residue conservation analysis

PDB id:

2ffw

Name:

Ligase

Title:

Solution structure of the rbcc/trim b-box1 domain of human mid1: b-box with a ring

Structure:

Midline-1. Chain: a. Fragment: b-box 1 domain (residues: 87 - 164). Synonym: tripartite motif protein 18, putative transcription factor xprf, midin, ring finger protein 59. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mid1, fxy, rnf59, trim18, xprf. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

13 models

Authors:

M.A.Massiah,B.N.Simmons,K.M.Short,T.C.Cox

Key ref:

M.A.Massiah et al. (2006). Solution structure of the RBCC/TRIM B-box1 domain of human MID1: B-box with a RING. J Mol Biol, 358, 532-545. PubMed id: 16529770 DOI: 10.1016/j.jmb.2006.02.009

Date:

20-Dec-05 Release date: 09-May-06

Protein chain

O15344  (TRI18_HUMAN) -  E3 ubiquitin-protein ligase Midline-1 from Homo sapiens

Seq: 667 a.a.

Struc: 78 a.a.

Enzyme reactions

• Enzyme class: E.C.2.3.2.27 - RING-type E3 ubiquitin transferase.
• Reaction: S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N₆- ubiquitinyl-[acceptor protein]-L-lysine

DOI no: 10.1016/j.jmb.2006.02.009

J Mol Biol 358:532-545 (2006)

PubMed id: 16529770

Solution structure of the RBCC/TRIM B-box1 domain of human MID1: B-box with a RING.

M.A.Massiah, B.N.Simmons, K.M.Short, T.C.Cox.

ABSTRACT

B-box domains are a defining feature of the tripartite RBCC (RING, B-box, coiled-coil) or TRIM proteins, many of which are E3 ubiquitin ligases. However, little is known about the biological function of B-boxes. In some RBCC/TRIM proteins there is only a single B-box (type 2) domain, while others have both type 1 and type 2 B-box domains in tandem adjacent to their RING domain. These two types of B-boxes share little sequence similarity, except the presence of cysteine and histidine residues: eight in most B-box1 domains and seven in B-box2 domains. We report here the high-resolution solution structure of the first B-box1 domain (from the human RBCC protein, MID1) based on 670 nuclear Overhauser effect (NOE)-derived distance restraints, 12 hydrogen bonds, and 44 dihedral angles. The domain consists of a three-turn alpha-helix, two short beta-strands, and three beta-turns, encompassing Val117 to Pro164, which binds two zinc atoms. One zinc atom is coordinated by cysteine residues 119, 122, 142, 145, while cysteine 134, 137 and histidine 150, 159 coordinate the other. This topology is markedly different from the only other B-box structure reported; that of a type 2 B-box from Xenopus XNF7, which binds a single zinc atom. Of note, the B-box1 structure closely resembles the folds of the RING, ZZ and U-box domains of E3 and E4 ubiquitin enzymes, raising the possibility that the B-box1 domain either has E3 activity itself or enhances the activity of RING type E3 ligases (i.e. confers E4 enzyme activity). The structure of the MID1 B-box1 also reveals two potential protein interaction surfaces. One of these is likely to provide the binding interface for Alpha 4 that is required for the localized turnover of the catalytic subunit of PP2A, the major Ser/Thr phosphatase.

Selected figure(s)

Figure 5.
Figure 5. Surface representation of B-box1 showing basic patches (colored blue) comprised of lysine and arginine residues, acidic patches of glutamic and aspartic acids (colored red), and hydrophobic surfaces (colored green) formed by leucine, isoleucine, alanine, phenylalanine, and valine residues. The red arrow indicates a cleft formed by two acidic residues flanking a hydrophobic pocket. The blue arrow indicates a large cleft of basic residues that may be important for protein–protein interaction (possibly with Alpha 4).

Figure 6.
Figure 6. Structural similarities between B-box1, RING, U-box and ZZ domains. (a) Ribbon representation of RING domains from the breast cancer susceptibility protein, BRCA1 (1JM7), CDK-activating kinase assembly factor, MAT1 (1G25), a schematic representation of a canonical RING structure, the U-box domain from E4A, the ZZ domain from CBP/p300, and the B-box1 domain from MID1. (b) Consensus zinc-binding motifs of RING, ZZ, U-box and B-box1 domains; X=any amino acid, C and H are cysteine and histidine, zinc-binding residues.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 358, 532-545) copyright 2006.

Figures were selected by an automated process.