1vry
From Proteopedia
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Second and Third Transmembrane Domains of the Alpha-1 Subunit of Human Glycine Receptor
Contents |
Overview
A 61-residue polypeptide resembling the second and third transmembrane domains (TM23) of the alpha-1 subunit of human glycine receptor and its truncated form, both with the wild-type loop linking the two TM domains (the "23" loop), were studied using high-resolution NMR. Well-defined domain structures can be identified for the TM2, 23 loop, and TM3 regions. Contrary to the popular model of a long and straight alpha-helical structure for the pore-lining TM2 domain for the Cys-loop receptor family, the last three residues of the TM2 domain and the first eight residues of the 23 loop (S16-S26) seem to be intrinsically nonhelical and highly flexible even in trifluoroethanol, a solvent known to promote and stabilize alpha-helical structures. The six remaining residues of the 23 loop and most of the TM3 domain exhibit helical structures with a kinked pi-helix (or a pi-turn) from W34 to C38 and a kink angle of 159 +/- 3 degrees . The tertiary fold of TM3 relative to TM2 is defined by several unambiguously identified long-range NOE cross-peaks within the loop region and between TM2 and TM3 domains. The 20 lowest-energy structures show a left-handed tilt of TM3 relative to TM2 with a tilting angle of 44 +/- 2 degrees between TM2 (V1-Q14) and TM3 (L39-E48) helix axes. This left-handed TM2-TM3 arrangement ensures a neatly packed right-handed quaternary structure of five subunits to form an ion-conducting pore. This is the first time that two TM domains of the glycine receptor linked by the important 23 loop have ever been analyzed at atomistic resolution. Many structural characteristics of the receptor can be inferred from the structural and dynamical features identified in this study.
Disease
Known diseases associated with this structure: Hyperekplexia and spastic paraparesis OMIM:[138491], Startle disease, autosomal recessive OMIM:[138491], Startle disease/hyperekplexia, autosomal dominant OMIM:[138491]
About this Structure
1VRY is a Single protein structure of sequence from Homo sapiens. This structure supersedes the now removed PDB entry 1ZHD. Full crystallographic information is available from OCA.
Reference
Structure and dynamics of the second and third transmembrane domains of human glycine receptor., Ma D, Liu Z, Li L, Tang P, Xu Y, Biochemistry. 2005 Jun 21;44(24):8790-800. PMID:15952785
Page seeded by OCA on Thu Feb 21 15:38:01 2008
