PDBsum entry 4fe8

Signaling protein

PDB id: 4fe8

Contents

Protein chain

402 a.a.

Metals

_ZN ×31

Waters ×148

PDB id:

4fe8

Name:

Signaling protein

Title:

Crystal structure of htt36q3h-ex1-x1-c1(alpha)

Structure:

Maltose-binding periplasmic protein,huntingtin. Chain: a, b, c. Fragment: huntingtin protein exon1 domain (unp residues 1-164), huntingtin protein exon1 domain (unp residues 1-164). Synonym: mbp,mmbp,maltodextrin-binding protein,huntington disease protein,hd protein. Engineered: yes. Mutation: yes

Source:

Escherichia coli (strain k12), homo sapiens. Human. Organism_taxid: 83333, 9606. Strain: k12. Gene: male, b4034, jw3994, htt, hd, it15. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

3.00Å R-factor: 0.229 R-free: 0.275

Authors:

M.Kim

Key ref:

M.Kim (2013). Beta conformation of polyglutamine track revealed by a crystal structure of Huntingtin N-terminal region with insertion of three histidine residues. Prion, 7, 221-228. PubMed id: 23370273 DOI: 10.4161/pri.23807

Date:

29-May-12 Release date: 13-Mar-13

Protein chains

P0AEX9  (MALE_ECOLI) -  Maltose/maltodextrin-binding periplasmic protein from Escherichia coli (strain K12)

Seq: 396 a.a.

Struc: 402 a.a.*

Protein chains

P42858  (HD_HUMAN) -  Huntingtin from Homo sapiens

Seq: 3142 a.a.

Struc: 402 a.a.*

* PDB and UniProt seqs differ at 10 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.4161/pri.23807

Prion 7:221-228 (2013)

PubMed id: 23370273

Beta conformation of polyglutamine track revealed by a crystal structure of Huntingtin N-terminal region with insertion of three histidine residues.

M.Kim.

ABSTRACT

Huntington disease is an autosomal-dominant neurodegenerative disorder caused by a polyglutamine (polyQ) expansion (> 35Q) in the first exon (EX1) of huntingtin protein (Htt). mHtt protein is thought to adopt one or more toxic conformation(s) that are involved in pathogenic interactions in cells . However, the structure of mHtt is not known. Here, we present a near atomic resolution structure of mHtt36Q-EX1. To facilitate crystallization, three histidine residues (3H) were introduced within the Htt36Q stretch resulting in the sequence of Q 7HQHQHQ 27. The Htt36Q3H region adopts α-helix, loop, β-hairpin conformations. Furthermore, we observed interactions between the backbone of the Htt36Q3H β-strand with the aromatic residues mimicking putative-toxic interactions with other proteins. Our findings support previous predictions that the expanded mHtt-polyQ region adopts a β-sheet structure. Detailed structural information about mHtt improves our understanding of the pathogenic mechanisms in HD and other polyQ expansion disorders and may form the basis for rational design of small molecules that target toxic conformations of disease-causing proteins.