Table 5.

Role and localization of residues in ECL1 as determined by mutagenesis studies

Classification	Claudin-1* (59)	Claudin-2+ (17, 416)	Claudin-4 (57, 146)	Claudin-5 (395)	Claudin-7 (6)	Claudin-10a (373)	Claudin-15 (57)	Claudin-16 (143)	Claudin-17 (196)
F	R31A no effect on HCV entry		R31T no effect
E	Y35A no effect on HCV entry	Y35C located at vestibule				R32D reduce Cl− selectivity
C?	D38A abolish HCV entry				D38R reduce Cl− barrier			D104S reduce Na+ selectivity
F								D105S reduce Na+ selectivity slightly
F								E108T no effect
F			E48Q no effect				E46K no effect	R114T no effect
B	G49A abolish HCV entry
B	L50A abolish HCV entry
B	W51A abolish HCV entry
F	S53A no effect on HCV entry	E53Q no effect			E53K reduce Cl− barrier slightly			E119T reduce Na+ selectivity slightly
B	C54A abolish HCV entry			C54S loss of Na+ barrier
E		H57C located at vestibule					D55R confer Cl− selectivity
B	C64A abolish HCV entry			C64S loss of Na+ and mannitol barrier
C		D65N abolish Na+ binding site	K65D, K65T confer Na+ selectivity			R59D reduce Cl− selectivity	E64K confer Cl− selectivity	D132S no effect	K65E and K65A abolish Cl− selectivity
D		I66C exposed to pore lumen						E133T no effect
F			D68N no effect					D135S no effect
F		D76N no effect	D76N no effect
A			R81T weak ER expression					R149L/T weak ER expression

Classification refers to tentative assignment of role at each position: A, conserved residue essential for expression, trafficking, and presumably for global protein folding; B, conserved residue essential for claudin function at the plasma membrane; C, charged residue that acts as intrapore binding site; D, other pore-lining residue; E, residue at vestibule which may confer surface charge effects; F, residue that appears nonessential.

^*Claudin function assessed by ability to mediate cellular entry of hepatitis C virus (HCV).

⁺Residue locations inferred based on accessibility to and block by methanethiosulfonate reagents. Reference numbers are given in parentheses.