PDBsum entry 2msv

Membrane protein

PDB id: 2msv

Contents

Protein chain

154 a.a.

PDB id:

2msv

Name:

Membrane protein

Title:

Solution structure of the mlkl n-terminal domain

Structure:

Mixed lineage kinase domain-like protein. Chain: a. Fragment: n-terminal domain, residues 1-154. Synonym: hmlkl. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mlkl. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

L.Su,J.Rizo,B.Quade,H.Wang,L.Sun,X.Wang

Key ref:

L.Su et al. (2014). A plug release mechanism for membrane permeation by MLKL. Structure, 22, 1489-1500. PubMed id: 25220470 DOI: 10.1016/j.str.2014.07.014

Date:

07-Aug-14 Release date: 24-Sep-14

Protein chain

Q8NB16  (MLKL_HUMAN) -  Mixed lineage kinase domain-like protein from Homo sapiens

Seq: 471 a.a.

Struc: 154 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/j.str.2014.07.014

Structure 22:1489-1500 (2014)

PubMed id: 25220470

A plug release mechanism for membrane permeation by MLKL.

L.Su, B.Quade, H.Wang, L.Sun, X.Wang, J.Rizo.

ABSTRACT

MLKL is crucial for necroptosis, permeabilizing membranes through its N-terminal region upon phosphorylation of its kinase-like domain by RIP3. However, the mechanism underlying membrane permeabilization is unknown. The solution structure of the MLKL N-terminal region determined by nuclear magnetic resonance spectroscopy reveals a four-helix bundle with an additional helix at the top that is likely key for MLKL function, and a sixth, C-terminal helix that interacts with the top helix and with a poorly packed interface within the four-helix bundle. Fluorescence spectroscopy measurements indicate that much of the four-helix bundle inserts into membranes, but not the C-terminal helix. Moreover, we find that the four-helix bundle is sufficient to induce liposome leakage and that the C-terminal helix inhibits this activity. These results suggest that the four-helix bundle mediates membrane breakdown during necroptosis and that the sixth helix acts as a plug that prevents opening of the bundle and is released upon RIP3 phosphorylation.