Recent structural studies suggest that GLUT1 (glucose transporter 1)-mediated sugar transport is mediated by an alternating access transporter that successively presents exofacial (e2) and endofacial (e1) substrate-binding sites. Transport studies, however, indicate multiple, interacting (allosteric), and co-existent, exo- and endofacial GLUT1 ligand-binding sites. The present study asks whether these contradictory conclusions result from systematic analytical error or reveal a more fundamental relationship between transporter structure and function. Here, homology modeling supported the alternating access transporter model for sugar transport by confirming at least four GLUT1 conformations, the so-called outward, outward-occluded, inward-occluded, and inward GLUT1 conformations. Results from docking analysis suggested that outward and outward-occluded conformations present multiple β-d-glucose and maltose interaction sites, whereas inward-occluded and inward conformations present only a single β-d-glucose interaction site. Gln-282 contributed to sugar binding in all GLUT1 conformations via hydrogen bonding. Mutating Gln-282 to alanine (Q282A) doubled the Km(app) for 2-deoxy-d-glucose uptake and eliminated cis-allostery (stimulation of sugar uptake by subsaturating extracellular maltose) but not trans-allostery (uptake stimulation by subsaturating cytochalasin B). cis-Allostery persisted, but trans-allostery was lost in an oligomerization-deficient GLUT1 variant in which we substituted membrane helix 9 with the equivalent GLUT3 sequence. Moreover, Q282A eliminated cis-allostery in the oligomerization variant. These findings reconcile contradictory conclusions from structural and transport studies by suggesting that GLUT1 is an oligomer of allosteric, alternating access transporters in which 1) cis-allostery is mediated by intrasubunit interactions and 2) trans-allostery requires intersubunit interactions.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2BysegX
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Family: Know the drill New Straits Times Online One of my sons had this so often that his tonsils were removed. ... However, for som...
-
Publication date: Available online 2 November 2017 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology Author(s): Ton...
-
UM-Chor1: establishment and characterization of the first validated clival chordoma cell line. J Neurosurg. 2017 Apr 21;:1-9 Authors:...
-
Publication date: Available online 10 May 2017 Source: Journal of Dairy Science Author(s): R.E. Vibart, M. Tavendale, D. Otter, B.H. Schw...
-
A 47-year-old woman presented with a 4-week history of progressive loss of vision, first manifesting as night blindness. Additionally, the p...
-
Abstract Cerebral and systemic organ microvascular pathologies coexist with human Alzheimer’s disease (AD) neuropathology. In this study, w...
-
Related Articles Developmental control of macrophage function. Curr Opin Immunol. 2017 Dec 13;50:64-74 Authors: Bonnardel J, Guillia...
-
Description A Caucasian boy aged 5 years presented with acute onset of a non-tender, palpable purpuric rash to his lower limbs, preceded by ...
-
Abstract: Epidermolytic ichthyosis (EI) is a rare disorder of cornification caused by mutations in KRT1 and KRT10, encoding two suprabasal e...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου