Residues R282 and D341 act as electrostatic gates in the proton-dependent oligopeptide transporter PepT1.
The oligopeptide transporter PepT1 is a protein found in the membrane of the cells of the intestinal walls, and represents the main route through which proteic nutrients are absorbed by the organism. Along the polypeptidic chain of this protein, two oppositely charged amino acids, an arginine in position 282 and an aspartate in position 341 of the sequence, have been hypothesised to form a barrier in the absorption pathway. In this paper we show that appropriate mutations of these amino acids change the properties of PepT1 in a way that confirms that these parts of the protein indeed act as an electrostatic gate in the transport process. The identification of the structural basis of the functional mechanism of this transporter is important because, in addition to its role in nutrient uptake, PepT1 represents a major pathway for the absorption of several therapeutic drugs.
Department of Biotechnology and Molecular Sciences, University of Insubria, Varese, Italy.
Elena
E
Bossi
Maria Daniela
MD
Renna
Rachele
R
Sangaletti
Francesca
F
D'Antoni
Francesca
F
Cherubino
Gabor
G
Kottra
Antonio
A
Peres
D019943:Amino Acid Substitution / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000502:physiology*; D001224:Aspartic Acid / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism; D055724:Electrophysiological Phenomena / Q000502:physiology; D005260:Female; D006639:Histidine / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D000074011:Peptide Transporter 1; D011522:Protons; D018075:RNA, Complementary / Q000235:genetics; D011817:Rabbits; D055672:Static Electricity; D027981:Symporters / Q000502:physiology*; D014982:Xenopus laevis
D004151:Dipeptides; D000074011:Peptide Transporter 1; D011522:Protons; D018075:RNA, Complementary; D027981:Symporters; C437951:lysylglycine; C039788:glycylglutamine; D001224:Aspartic Acid; C017033:aspartylglycine; D006639:Histidine; D001120:Arginine