7yr5

From Proteopedia

Embigin facilitates monocarboxylate transporter 1 localization to plasma membrane and transition to a decoupling state

Structural highlights

7yr5 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.63Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

EMB_HUMAN Plays a role in the outgrowth of motoneurons and in the formation of neuromuscular junctions. Following muscle denervation, promotes nerve terminal sprouting and the formation of additional acetylcholine receptor clusters at synaptic sites without affecting terminal Schwann cell number or morphology. Delays the retraction of terminal sprouts following re-innervation of denervated endplates. May play a role in targeting the monocarboxylate transporters SLC16A1, SLC16A6 and SLC16A7 to the cell membrane (By similarity).[UniProtKB:O88775]

Publication Abstract from PubMed

Cell-surface ancillary glycoproteins basigin or embigin form heterodimeric complexes with proton-coupled monocarboxylate transporters (MCTs), facilitating the membrane trafficking of MCTs and regulating their transport activities. Here, we determine the cryoelectron microscopy (cryo-EM) structure of the human MCT1-embigin complex and observe that embigin forms extensive interactions with MCT1 to facilitate its localization to the plasma membrane. In addition, the formation of the heterodimer effectively blocks MCT1 from forming a homodimer through a steric hindrance effect, releasing the coupling between two signature motifs and driving a significant conformation change in transmembrane helix 5 (TM5) of MCTs. Consequently, the substrate-binding pocket alternates between states of homodimeric coupling and heterodimeric decoupling states and exhibits differences in substrate-binding affinity, supporting the hypothesis that the substrate-induced motion originating in one subunit of the MCT dimer could be transmitted to the adjacent subunit to alter its substrate-binding affinity.

Embigin facilitates monocarboxylate transporter 1 localization to the plasma membrane and transition to a decoupling state.,Xu B, Zhang M, Zhang B, Chi W, Ma X, Zhang W, Dong M, Sheng L, Zhang Y, Jiao W, Shan Y, Chang W, Wang P, Wen S, Pei D, Chen L, Zhang X, Yan H, Ye S Cell Rep. 2022 Sep 13;40(11):111343. doi: 10.1016/j.celrep.2022.111343. PMID:36103816^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Xu B, Zhang M, Zhang B, Chi W, Ma X, Zhang W, Dong M, Sheng L, Zhang Y, Jiao W, Shan Y, Chang W, Wang P, Wen S, Pei D, Chen L, Zhang X, Yan H, Ye S. Embigin facilitates monocarboxylate transporter 1 localization to the plasma membrane and transition to a decoupling state. Cell Rep. 2022 Sep 13;40(11):111343. doi: 10.1016/j.celrep.2022.111343. PMID:36103816 doi:http://dx.doi.org/10.1016/j.celrep.2022.111343