PDBsum entry 6cse

Membrane protein

PDB id: 6cse

Contents

Protein chains

214 a.a.

213 a.a.

431 a.a.

Ligands

ALA

Metals

_NA

PDB id:

6cse

Name:

Membrane protein

Title:

Crystal structure of sodium/alanine symporter agcs with l-alanine bound

Structure:

Monoclonal antibody fab heavy chain. Chain: a, h. Monoclonal antibody fab light chain. Chain: b, l. Sodium/alanine symporter agcs. Chain: m, c. Synonym: alanine permease. Engineered: yes

Source:

Mus musculus. Organism_taxid: 10090. Methanococcus maripaludis (strain s2 / ll). Organism_taxid: 267377. Strain: s2 / ll. Gene: agcs, mmp1511. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

3.24Å R-factor: 0.231 R-free: 0.251

Authors:

J.Ma,F.E.Reyes,T.Gonen

Key ref:

J.Ma et al. (2019). Structural basis for substrate binding and specificity of a sodium-alanine symporter AgcS. Proc Natl Acad Sci U S A, 116, 2086-2090. PubMed id: 30659158 DOI: 10.1073/pnas.1806206116

Date:

20-Mar-18 Release date: 30-Jan-19

Protein chains

No UniProt id for this chain

Struc: 214 a.a.

Protein chains

No UniProt id for this chain

Struc: 213 a.a.

Protein chains

Q6LX42  (AGCS_METMP) -  Sodium/alanine symporter AgcS from Methanococcus maripaludis (strain DSM 14266 / JCM 13030 / NBRC 101832 / S2 / LL)

Seq: 453 a.a.

Struc: 431 a.a.

DOI no: 10.1073/pnas.1806206116

Proc Natl Acad Sci U S A 116:2086-2090 (2019)

PubMed id: 30659158

Structural basis for substrate binding and specificity of a sodium-alanine symporter AgcS.

J.Ma, H.T.Lei, F.E.Reyes, S.Sanchez-Martinez, M.F.Sarhan, J.Hattne, T.Gonen.

ABSTRACT

The amino acid, polyamine, and organocation (APC) superfamily is the second largest superfamily of membrane proteins forming secondary transporters that move a range of organic molecules across the cell membrane. Each transporter in the APC superfamily is specific for a unique subset of substrates, even if they possess a similar structural fold. The mechanism of substrate selectivity remains, by and large, elusive. Here, we report two crystal structures of an APC member from Methanococcus maripaludis, the alanine or glycine:cation symporter (AgcS), with l- or d-alanine bound. Structural analysis combined with site-directed mutagenesis and functional studies inform on substrate binding, specificity, and modulation of the AgcS family and reveal key structural features that allow this transporter to accommodate glycine and alanine while excluding all other amino acids. Mutation of key residues in the substrate binding site expand the selectivity to include valine and leucine. These studies provide initial insights into substrate selectivity in AgcS symporters.