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			PubMed Journals: Biochemistry

  Source:		PMID: 7578066


    		Biochemistry. 1995 Nov 7;34(44):14594-600.
     
			Preferred sites of glycosylphosphatidylinositol
			modification in folate receptors and constraints
			in the primary structure of the hydrophobic
			portion of the signal.

			Yan W(1), Ratnam M.

			Author Information
			(1) Department of Biochemistry and Molecular
			Biology, Medical College of Ohio, Toledo
			43699-0008, USA.

			The divergent carboxyl-terminal signal peptides for
			glycosylphosphatidylinositol (GPI) membrane
			anchor attachment in folate receptor (FR)
			types alpha and beta were characterized.
			All of the candidate amino acid residues
			for GPI modification were identified and
			tested by substituting individually and
			in combination with amino acids that cannot
			be modified by GPI. Thus the GPI modification
			in FR-alpha was decreased to 22% by mutation
			of Ser234 to Thr but unaltered by changing
			the other candidate, Gly235, to Met. However,
			the double mutant FR-alpha Ser234-Thr,Gly235-Met
			showed half of the GPI modification seen
			in FR-alpha Ser234-Thr. This result suggests
			that Ser234 is the preferred GPI modification
			site, while Gly235 is a minor, alternate
			GPI modification site. Similarly, in FR-beta,
			mutation of Asn230 to Gln decreased GPI
			modification to 32%, while mutation of the
			other candidate site, Gly237, to Met had
			no effect. However, mutation at both sites
			further reduced the GPI modification by
			a half. A five amino acid carboxyl-terminal
			deletion (FR-beta delta 5) caused no decrease
			in the extent of GPI modification. However,
			the same deletion in FR beta Asn230-Gln
			decreased the residual GPI modification
			by 66%. These results suggest that Asn230
			is the preferred GPI modification site in
			FR-beta, while Gly235 offers a minor alternate
			modification site; consistent with this
			conclusion is the fact that modification
			at the downstream site is hindered by its
			proximity to the carboxyl terminus in FR-beta
			delta 5. Further, the suggestion that the
			hydrophobic portion of the GPI signal is
			a random sequence of neutral amino acids
			with overall moderate hydrophobicity was
			tested.(ABSTRACT TRUNCATED AT 250 WORDS)

			PMID: 7578066 [Indexed for MEDLINE]

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