Modular arrangement of extracellular regions and protein superfamilies

The extracellular regions of immune cell surface proteins include distinct domains which are often connected to the transmembrane domain by a linker or stalk region. Only one or two domains may have specific binding functions. Others may trigger oligomerization or ensure that binding domains are sufficiently distant from the membrane. Many extracellular protein modules belong to superfamilies. By definition, members of protein superfamilies share limited sequence similarity, often 30% or less, but similar three-dimensional structures. Table 1 includes structural prototypes of superfamilies determined to date. Some small domains found in different cell surface proteins consist of ß sheets or hairpins which may be arranged sandwich-like and stabilized by disulfide bonds.

Table 1 Three-dimensional structures of immune cell surface receptors and adhesion molecules

EGR6 FN type lao FN type 11*6

CD2 (domain 1)c CD2 (domains 1 + 2)c CD2 (domain 1, glycosylated)8 FN type III8-6" FN type III

FN type III (domains 7-10) hGH/hGHR" complex hGH/hPRLR" complex CCP (two domains)"'6 TNFR/TNFp complex TNFR NFcR

NFcR/Fc complex

E-selectin (C-type lectin + EGF domains) CD59 (glycosylated)3 Tissue factor"

Tissue factor/FVIIa complex

Integrin CD11b/CD18 (A domain, Mg2+ form)

Integrin CD11b/CD18 (A domain, Mn2' form)


cbEGF (two domains) TCR (V(1 + Cp domains)1 TCR (V„ domain)0 IFN7/IFN7R« complex" E-Cadherin (domain 1)"" N-Cadherin (domain 1)" E-Cadherin (domains 1 + 2)" LM-EGF (three domains)6 TCR/MHC class I complex^ TCR/MHC class I complex11 EPOR/peptide complex" Link domain3 NCAM (domain I)« ICAM-2 (domains 1 + 2)c IL-1R/IL-1/3 complex* IL-1R/IL-1RA complex0 CD4 (domains 1-4) CD8a/MHC class I complex

Cooke et aI (1987) Nature 327: 339

Baron et al (1990) Nature 345: 642

Constantine et al (1992) J Mol Biol 223: 281

Rye et al (1990) Nature 348: 419

Wang et al (1990) Nature 348: 411

Brady et al (1993) Science 260: 979

Leahy et al (1992) Cell 68: 1145

Driscoll et al (1991) Nature 353: 762

Jones et al (1992) Nature 360: 232

Whitka etal (1993) Structure 1: 69

Main et al (1992) Cell 71: 671

Leahy et al (1992) Science 258: 987

Leahy et al (1996) Cell 84: 155

De Vos et al (1992) Science 255: 306

Somers et al (1994) Nature 372: 478

Barlow et al (1993) J Mol Biol 232: 268

Banner et al (1993) Cell 73: 431

Naismith ef al (1995) J Biol Chem 270: 13303

Burmeister et al (1994) Nature 372: 336

Burmeister et al (1994) Nature 372: 379

Graves et al (1994) Nature 367: 532

Fletcher et al (1994) Structure 2: 185

Harlos et al (1994) Nature 370: 662

Banner et al (1996) Nature 380: 41

Jones et al (1995) Nature 373: 539

Lee et al (1995) Structure 3: 1333

Downing et al (1996) Cell 85: 597

Bentley et al (1995) Science 267: 1984

Fields et al (1995) Science 270: 1821

Walter et al (1995) Nature 376: 230

Overduin et al (1995) Science 267: 386

Shapiro et al (1995) Nature 374: 327

Nagar et al (1996) Nature 380: 360

Stetefeld et al (1996) J Mol Biol 257: 644

Garcia et al (1996) Science 274: 209

Garboczi etal (1996) Nature 384: 134

Livnah etal (1996) Science 273: 464

Kohda et al (1996) Cell 86: 767

Thomsen et al (1996) Nature Struct Biol 3: 581

Casanovas etal (1997) Nature 387: 312

Vigers et al (1997) Nature 386: 190

Schreuder et al (1997) Nature 386: 194

Wu et al (1997) Nature 387: 527

Gao et al (1997) Nature 387: 630

C, constant; CCP, complement control protein; C-type, calcium-dependent; EGF, epidermal growth factor; cbEGF, calcium-binding epidermal growth factor; EOPR, Erythropoietin receptor; FVIIa, blood coagulation factor Vila; Fc, antibody constant fragment; FN, fibronectin; hGH, human growth hormone; hGHR, human growth hormone receptor; hPRLR, human prolactin receptor; ICAM, intercellular adhesion molecule; IL-1R, interleukin-1 receptor; IL-1RA, interleukin-1 receptor antagonist; I FN, interferon; IFN-yRa, high-affinity interferon y receptor; LM-EGF, laminin-type EGF-like; NCAM, neural cell adhesion molecule; NFcR, neonatal fc receptor; TCR, T cell receptor; TNF, tumor necrosis factor: TNFR, tumor necrosis factor receptor; V, variable; VCAM-1, vascular cell adhesion molecule 1. "Structures determined by NMR.

"Small domains which occur in many cell surface or extracellular matrix proteins. "Immunoglobulin superfamily (IgSF) members. "Structurally similar to IgSF domains.

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