Self-association of human immunoglobulin κI light chains

Role of the third hypervariable region

F. J. Stevens, F. A. Westholm, Alan Solomon, M. Schiffer

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Gel electrophoresis and molecular sieve chromatography were used to compare 17 different human κI type Bence Jones proteins including 5 for which the amino acid sequence is known. Although electrophoresis in the presence of NaDodSO4 showed uniformity of covalent dimer and monomer molecular weights, Sephadex chromatography under nondissociating conditions showed that monomers eluted with different apparent molecular weights. These differences were attributed to heterogeneity in light chain self-association; dimerization constants of the 17 proteins, calculated from a computer simulation of their behavior upon gel filtration, ranged from <103 to >106 M-1. The variable region, more specifically the third hypervariable region, appears to be responsible for the variation in the dimerization constant. Association properties of light chains of known sequence suggest that the presence of an aromatic or hydrophobic residue at position 96 enhances dimer formation whereas a charged residue at that position results in light chains remaining stable monomers. The location of hypervariable residue 96 within the amino-terminal portion of the joining segment of the variable region suggests that the joining region may account for the variability of self-association of light chains and, moreover, that it has a function in determining the selective association of immunoglobulin polypeptide chains.

Original languageEnglish (US)
Pages (from-to)1144-1148
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume77
Issue number2 II
StatePublished - Dec 1 1980
Externally publishedYes

Fingerprint

Immunoglobulin Light Chains
Light
Dimerization
Gel Chromatography
Electrophoresis
Immunoglobulin Subunits
Molecular Weight
Bence Jones Protein
Computer Simulation
Chromatography
Amino Acid Sequence
Gels
Proteins

All Science Journal Classification (ASJC) codes

  • General
  • Genetics

Cite this

Self-association of human immunoglobulin κI light chains : Role of the third hypervariable region. / Stevens, F. J.; Westholm, F. A.; Solomon, Alan; Schiffer, M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 77, No. 2 II, 01.12.1980, p. 1144-1148.

Research output: Contribution to journalArticle

@article{4979dac911664ca3975e389f811ba9a4,
title = "Self-association of human immunoglobulin κI light chains: Role of the third hypervariable region",
abstract = "Gel electrophoresis and molecular sieve chromatography were used to compare 17 different human κI type Bence Jones proteins including 5 for which the amino acid sequence is known. Although electrophoresis in the presence of NaDodSO4 showed uniformity of covalent dimer and monomer molecular weights, Sephadex chromatography under nondissociating conditions showed that monomers eluted with different apparent molecular weights. These differences were attributed to heterogeneity in light chain self-association; dimerization constants of the 17 proteins, calculated from a computer simulation of their behavior upon gel filtration, ranged from <103 to >106 M-1. The variable region, more specifically the third hypervariable region, appears to be responsible for the variation in the dimerization constant. Association properties of light chains of known sequence suggest that the presence of an aromatic or hydrophobic residue at position 96 enhances dimer formation whereas a charged residue at that position results in light chains remaining stable monomers. The location of hypervariable residue 96 within the amino-terminal portion of the joining segment of the variable region suggests that the joining region may account for the variability of self-association of light chains and, moreover, that it has a function in determining the selective association of immunoglobulin polypeptide chains.",
author = "Stevens, {F. J.} and Westholm, {F. A.} and Alan Solomon and M. Schiffer",
year = "1980",
month = "12",
day = "1",
language = "English (US)",
volume = "77",
pages = "1144--1148",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "2 II",

}

TY - JOUR

T1 - Self-association of human immunoglobulin κI light chains

T2 - Role of the third hypervariable region

AU - Stevens, F. J.

AU - Westholm, F. A.

AU - Solomon, Alan

AU - Schiffer, M.

PY - 1980/12/1

Y1 - 1980/12/1

N2 - Gel electrophoresis and molecular sieve chromatography were used to compare 17 different human κI type Bence Jones proteins including 5 for which the amino acid sequence is known. Although electrophoresis in the presence of NaDodSO4 showed uniformity of covalent dimer and monomer molecular weights, Sephadex chromatography under nondissociating conditions showed that monomers eluted with different apparent molecular weights. These differences were attributed to heterogeneity in light chain self-association; dimerization constants of the 17 proteins, calculated from a computer simulation of their behavior upon gel filtration, ranged from <103 to >106 M-1. The variable region, more specifically the third hypervariable region, appears to be responsible for the variation in the dimerization constant. Association properties of light chains of known sequence suggest that the presence of an aromatic or hydrophobic residue at position 96 enhances dimer formation whereas a charged residue at that position results in light chains remaining stable monomers. The location of hypervariable residue 96 within the amino-terminal portion of the joining segment of the variable region suggests that the joining region may account for the variability of self-association of light chains and, moreover, that it has a function in determining the selective association of immunoglobulin polypeptide chains.

AB - Gel electrophoresis and molecular sieve chromatography were used to compare 17 different human κI type Bence Jones proteins including 5 for which the amino acid sequence is known. Although electrophoresis in the presence of NaDodSO4 showed uniformity of covalent dimer and monomer molecular weights, Sephadex chromatography under nondissociating conditions showed that monomers eluted with different apparent molecular weights. These differences were attributed to heterogeneity in light chain self-association; dimerization constants of the 17 proteins, calculated from a computer simulation of their behavior upon gel filtration, ranged from <103 to >106 M-1. The variable region, more specifically the third hypervariable region, appears to be responsible for the variation in the dimerization constant. Association properties of light chains of known sequence suggest that the presence of an aromatic or hydrophobic residue at position 96 enhances dimer formation whereas a charged residue at that position results in light chains remaining stable monomers. The location of hypervariable residue 96 within the amino-terminal portion of the joining segment of the variable region suggests that the joining region may account for the variability of self-association of light chains and, moreover, that it has a function in determining the selective association of immunoglobulin polypeptide chains.

UR - http://www.scopus.com/inward/record.url?scp=0019187615&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0019187615&partnerID=8YFLogxK

M3 - Article

VL - 77

SP - 1144

EP - 1148

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 2 II

ER -