GlpF

glpF is a gene that encodes the glycerol uptake facilitator protein GlpF, found in Escherichia coli and many other bacteria. It encodes a membrane channel that aids the transport of glycerol across the inner bacterial membrane, enabling efficient glycerol utilization when glycerol is present as a carbon source. GlpF is part of the glycerol utilization operon glpFKRD and is commonly studied alongside GlpK (glycerol kinase) and GlpD (glycerol-3-phosphate dehydrogenase).

GlpF belongs to the major intrinsic protein (MIP) family, which includes aquaporins. Like other members of this family, GlpF is predicted to contain six transmembrane helices and two conserved NPA motifs that contribute to pore formation. Structural studies of GlpF reveal a narrow pore that supports glycerol passage, with residues forming an aromatic/arginine (ar/R) selectivity filter that contributes to glycerol specificity and limits permeation of other solutes.

Expression of glpF is regulated by GlpR, a repressor of the glpFKRD operon. In the presence of glycerol-3-phosphate, GlpR repression is relieved, permitting transcription of glpF along with glpK and glpD. The CRP–cAMP regulatory system can further modulate transcription under carbon-limited conditions, enhancing operon expression when glucose is scarce.

Functionally, GlpF increases glycerol uptake to feed the glycerol kinase–mediated pathway, converting glycerol to glycerol-3-phosphate for metabolism. Mutations in glpF can reduce glycerol uptake, while overexpression can improve glycerol utilization. GlpF homologs are widely distributed in bacteria, reflecting the conserved need for environmental glycerol transport.