PDBsum entry 1z6c

Blood clotting

PDB id: 1z6c

Contents

Protein chain

87 a.a. *

Metals

_CA ×2

Waters ×6

* Residue conservation analysis

PDB id:

1z6c

Name:

Blood clotting

Title:

Solution structure of an egf pair (egf34) from vitamin k-dependent protein s

Structure:

Vitamin k-dependent protein s. Chain: a. Fragment: egf modules 3 and 4. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pros1, pros. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

T.Drakenberg,H.Ghasriani,E.Thulin,A.M.Thamlitz,A.Muranyi,A.Annila, J.Stenflo

Key ref:

T.Drakenberg et al. (2005). Solution structure of the Ca2+-Binding EGF3-4 pair from vitamin K-dependent protein S: identification of an unusual fold in EGF3. Biochemistry, 44, 8782-8789. PubMed id: 15952784 DOI: 10.1021/bi050101f

Date:

22-Mar-05 Release date: 21-Jun-05

Protein chain

P07225  (PROS_HUMAN) -  Vitamin K-dependent protein S from Homo sapiens

Seq: 676 a.a.

Struc: 87 a.a.

DOI no: 10.1021/bi050101f

Biochemistry 44:8782-8789 (2005)

PubMed id: 15952784

Solution structure of the Ca2+-Binding EGF3-4 pair from vitamin K-dependent protein S: identification of an unusual fold in EGF3.

T.Drakenberg, H.Ghasriani, E.Thulin, A.M.Thämlitz, A.Muranyi, A.Annila, J.Stenflo.

ABSTRACT

Vitamin K-dependent protein S is a cofactor of activated protein C, a serine protease that regulates blood coagulation. Deficiency of protein S can cause venous thrombosis. Protein S has four EGF domains in tandem; domains 2-4 bind calcium with high affinity whereas domains 1-2 mediate interaction with activated protein C. We have now solved the solution structure of the EGF3-4 fragment of protein S. The linker between the two domains is similar to what has been observed in other calcium-binding EGF domains where it provides an extended conformation. Interestingly, a disagreement between NOE and RDC data revealed a conformational heterogeneity within EGF3 due to a hinge-like motion around Glu186 in the Cys-Glu-Cys sequence, the only point in the domain where flexibility is allowed. The dominant, bent conformation of EGF3 in the pair has no precedent among calcium-binding EGF domains. It is characterized by a change in the psi angle of Glu186 from 160 degrees +/- 40 degrees , as seen in ten other EGF domains, to approximately 0 degrees +/- 15 degrees . NOESY data suggest that Tyr193, a residue not conserved in other calcium-binding EGF domains (except in the homologue Gas6), induces the unique fold of EGF3. However, SAXS data, obtained on EGF1-4 and EGF2-4, showed a dominant, extended conformation in these fragments. This may be due to a counterproductive domain-domain interaction between EGF2 and EGF4 if EGF3 is in a bent conformation. We speculate that the ability of EGF3 to adopt different conformations may be of functional significance in protein-protein interactions involving protein S.