The solution structure of the pleckstrin homology domain of human SOS1

A possible structural role for the sequential association of DHL homology domain and pleckstrin homology domains

Jie Zheng, H. C. Chen, S. Corblan-Garcia, Sean M. Cahill, Dafna Bar-Sagi, David Cowburn

Research output: Contribution to journalArticle

Abstract

A large subset of Pleckstrin Homology (PH) domains are immediately to the ('terminus of Diffuse B cell lyphoma (Dbl) Homology (DbH) domains. Db! domains are generally considered to be GTPase exchange factors; many are protooncogenes. PH domains appear to function as membrane recruitment factors, or have specific protein-protein interactions. Since dual domain (DbH/PH) constructs are known to have significant properties in other pathways, it is pos Mble that a defined interdomain relationship is required for DbH/PH function. We determined the solution structure of the human SOSl PH domain for a construct partially extended in to the preceeding DbH domain. There are spe cific structural contacts between the PH and the vestigial DbH domain. This appears to involve structural elements of this subfamily of PH domains, and of DbH domains. The hSOSl PH domain binds to inositol(l,4,5)triphosphate with a c. 60 /xM affinity. Using chemical shift titration, the binding site is identified to be essentially identical to that observed crystallographically for the IP3 complex with the PH domain of PLC<5. While the overall fold of the hSOSl PH domain is similar to other PH domains, the size and position of the intrastrand loops and the presence of an N terminal a helix of the vestigial DbH domain suggest that the subfamily of PH domains associated with DbH domains may be a well-defined structural group in which the PH domain is a membrane recruiter and modulator.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number8
StatePublished - 1998
Externally publishedYes

Fingerprint

pleckstrin
sequence homology
Association reactions
platelet protein P47
Pleckstrin Homology Domains
Membranes
GTP Phosphohydrolases
Inositol
Chemical shift
Programmable logic controllers
proto-oncogenes
Titration
Proteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

@article{3398967422664d22a5072a874f17940e,
title = "The solution structure of the pleckstrin homology domain of human SOS1: A possible structural role for the sequential association of DHL homology domain and pleckstrin homology domains",
abstract = "A large subset of Pleckstrin Homology (PH) domains are immediately to the ('terminus of Diffuse B cell lyphoma (Dbl) Homology (DbH) domains. Db! domains are generally considered to be GTPase exchange factors; many are protooncogenes. PH domains appear to function as membrane recruitment factors, or have specific protein-protein interactions. Since dual domain (DbH/PH) constructs are known to have significant properties in other pathways, it is pos Mble that a defined interdomain relationship is required for DbH/PH function. We determined the solution structure of the human SOSl PH domain for a construct partially extended in to the preceeding DbH domain. There are spe cific structural contacts between the PH and the vestigial DbH domain. This appears to involve structural elements of this subfamily of PH domains, and of DbH domains. The hSOSl PH domain binds to inositol(l,4,5)triphosphate with a c. 60 /xM affinity. Using chemical shift titration, the binding site is identified to be essentially identical to that observed crystallographically for the IP3 complex with the PH domain of PLC<5. While the overall fold of the hSOSl PH domain is similar to other PH domains, the size and position of the intrastrand loops and the presence of an N terminal a helix of the vestigial DbH domain suggest that the subfamily of PH domains associated with DbH domains may be a well-defined structural group in which the PH domain is a membrane recruiter and modulator.",
author = "Jie Zheng and Chen, {H. C.} and S. Corblan-Garcia and Cahill, {Sean M.} and Dafna Bar-Sagi and David Cowburn",
year = "1998",
language = "English (US)",
volume = "12",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "8",

}

TY - JOUR

T1 - The solution structure of the pleckstrin homology domain of human SOS1

T2 - A possible structural role for the sequential association of DHL homology domain and pleckstrin homology domains

AU - Zheng, Jie

AU - Chen, H. C.

AU - Corblan-Garcia, S.

AU - Cahill, Sean M.

AU - Bar-Sagi, Dafna

AU - Cowburn, David

PY - 1998

Y1 - 1998

N2 - A large subset of Pleckstrin Homology (PH) domains are immediately to the ('terminus of Diffuse B cell lyphoma (Dbl) Homology (DbH) domains. Db! domains are generally considered to be GTPase exchange factors; many are protooncogenes. PH domains appear to function as membrane recruitment factors, or have specific protein-protein interactions. Since dual domain (DbH/PH) constructs are known to have significant properties in other pathways, it is pos Mble that a defined interdomain relationship is required for DbH/PH function. We determined the solution structure of the human SOSl PH domain for a construct partially extended in to the preceeding DbH domain. There are spe cific structural contacts between the PH and the vestigial DbH domain. This appears to involve structural elements of this subfamily of PH domains, and of DbH domains. The hSOSl PH domain binds to inositol(l,4,5)triphosphate with a c. 60 /xM affinity. Using chemical shift titration, the binding site is identified to be essentially identical to that observed crystallographically for the IP3 complex with the PH domain of PLC<5. While the overall fold of the hSOSl PH domain is similar to other PH domains, the size and position of the intrastrand loops and the presence of an N terminal a helix of the vestigial DbH domain suggest that the subfamily of PH domains associated with DbH domains may be a well-defined structural group in which the PH domain is a membrane recruiter and modulator.

AB - A large subset of Pleckstrin Homology (PH) domains are immediately to the ('terminus of Diffuse B cell lyphoma (Dbl) Homology (DbH) domains. Db! domains are generally considered to be GTPase exchange factors; many are protooncogenes. PH domains appear to function as membrane recruitment factors, or have specific protein-protein interactions. Since dual domain (DbH/PH) constructs are known to have significant properties in other pathways, it is pos Mble that a defined interdomain relationship is required for DbH/PH function. We determined the solution structure of the human SOSl PH domain for a construct partially extended in to the preceeding DbH domain. There are spe cific structural contacts between the PH and the vestigial DbH domain. This appears to involve structural elements of this subfamily of PH domains, and of DbH domains. The hSOSl PH domain binds to inositol(l,4,5)triphosphate with a c. 60 /xM affinity. Using chemical shift titration, the binding site is identified to be essentially identical to that observed crystallographically for the IP3 complex with the PH domain of PLC<5. While the overall fold of the hSOSl PH domain is similar to other PH domains, the size and position of the intrastrand loops and the presence of an N terminal a helix of the vestigial DbH domain suggest that the subfamily of PH domains associated with DbH domains may be a well-defined structural group in which the PH domain is a membrane recruiter and modulator.

UR - http://www.scopus.com/inward/record.url?scp=33749097087&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749097087&partnerID=8YFLogxK

M3 - Article

VL - 12

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 8

ER -