G proteins
AssigneeHeptares Therapeutics Limited
InventorsByron Carpenter, Andrew Leslie, Rony Nehmé, Christopher Gordon Tate, Antony Warne
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Abstract
The invention provides a mutant of a parent heterotrimeric G protein alpha (Gα) subunit, which mutant (i) lacks at least one helix of the helical domain of the parent Gα subunit; (ii) is capable of binding to a GPCR in the absence of a heterotrimeric G protein beta (Gβ) subunit and a heterotrimeric G protein gamma (Gγ) subunit; and (iii) has an amino acid sequence that contains one or more mutations compared to the amino acid sequence of the parent heterotrimeric Gα subunit, which mutations are selected from a deletion, a substitution and an insertion.
Claims26
An engineered mutant of a naturally-occurring parent heterotrimeric G protein alpha (Gα) subunit, which mutant:
- lacks the amino acid sequence of at least one of helix A (amino acids 85-113), helix B amino acids 123-136), helix C (amino acids 144-154), helix D (amino acids 157-168), helix E (amino acids 174-186), or helix F (amino acids 194-199) of the helical domain of the naturally-occurring parent Gα subunit, according to the numbering of the long isoform of human Gα-s subunit of SEQ ID NO:92;
- is capable of binding to a GPCR in the absence of a heterotrimeric G protein beta (Gβ) subunit and a heterotrimeric G protein gamma (Gγ) subunit;
- and
- has an amino acid sequence that contains one or more mutations compared to the amino acid sequence of the naturally-occurring parent heterotrimeric Gα subunit, which mutations are selected from a deletion, a substitution and an insertion;
- wherein binding of the mutant Gα subunit to a GPCR increases the affinity of the GPCR for an agonist.
Dependencies are inferred from the claim text.