PDBsum entry 4xu4

Unknown function

PDB id: 4xu4

Contents

Protein chain

189 a.a.

Ligands

BNG ×3

DDQ ×2

Waters ×98

PDB id:

4xu4

Name:

Unknown function

Title:

Crystal structure of a mycobacterial insig homolog mvins from mycobacterium vanbaalenii at 1.9a resolution

Structure:

Uncharacterized protein. Chain: a. Engineered: yes

Source:

Mycobacterium vanbaalenii pyr-1. Organism_taxid: 350058. Strain: pyr-1. Gene: mvan_1475. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.90Å R-factor: 0.186 R-free: 0.203

Authors:

R.B.Ren,J.P.Wu,C.Y.Yan,Y.He,N.Yan

Key ref:

R.Ren et al. (2015). PROTEIN STRUCTURE. Crystal structure of a mycobacterial Insig homolog provides insight into how these sensors monitor sterol levels. Science, 349, 187-191. PubMed id: 26160948 DOI: 10.1126/science.aab1091

Date:

25-Jan-15 Release date: 14-Oct-15

Protein chain

A1T557  (INSIG_MYCVP) -  INSIG protein homolog from Mycolicibacterium vanbaalenii (strain DSM 7251 / JCM 13017 / BCRC 16820 / KCTC 9966 / NRRL B-24157 / PYR-1)

Seq: 204 a.a.

Struc: 189 a.a.

DOI no: 10.1126/science.aab1091

Science 349:187-191 (2015)

PubMed id: 26160948

PROTEIN STRUCTURE. Crystal structure of a mycobacterial Insig homolog provides insight into how these sensors monitor sterol levels.

R.Ren, X.Zhou, Y.He, M.Ke, J.Wu, X.Liu, C.Yan, Y.Wu, X.Gong, X.Lei, S.F.Yan, A.Radhakrishnan, N.Yan.

ABSTRACT

Insulin-induced gene 1 (Insig-1) and Insig-2 are endoplasmic reticulum membrane-embedded sterol sensors that regulate the cellular accumulation of sterols. Despite their physiological importance, the structural information on Insigs remains limited. Here we report the high-resolution structures of MvINS, an Insig homolog from Mycobacterium vanbaalenii. MvINS exists as a homotrimer. Each protomer comprises six transmembrane segments (TMs), with TM3 and TM4 contributing to homotrimerization. The six TMs enclose a V-shaped cavity that can accommodate a diacylglycerol molecule. A homology-based structural model of human Insig-2, together with biochemical characterizations, suggest that the central cavity of Insig-2 accommodates 25-hydroxycholesterol, whereas TM3 and TM4 engage in Scap binding. These analyses provide an important framework for further functional and mechanistic understanding of Insig proteins and the sterol regulatory element-binding protein pathway.